tbuckley/cabot-search huggingface dataset:
HGS-TR2J, an agonistic, TRAIL receptor 2 monoclonal antibody, actively and rapidly stimulates the TRAIL receptor pathway that leads to significant inhibition of tumor growth in human tumor cell lines in vitro and in vivo
Authors: Robin C. Humphreys, Lindsey Shepard, Carol Poortman, Kathy McCormick, Clint Lincoln, Wendy Halpern, Paul Moore, Jim Fikes, Vivian Albert
Journal: Cancer Research (2005)

4388  Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) death receptors are abundantly expressed on the cell surface of a majority of human tumor cells. Activation of this pathway rapidly leads to programmed cell death. These characteristics make the TRAIL receptor (TRAIL-R) pathway an attractive target for cancer therapeutic agents. Binding of agonist monoclonal antibodies (mAbs) or the ligand TRAIL, to either functional death receptor (TRAIL-R1, TRAIL-R2) induces activation of a protease-mediated signaling cascade that culminates in programmed cell death. A fully human, agonist, TRAIL-R2 monoclonal antibody (mAb), HGS-TR2J (also known as KMTR-2), is being developed for use as a cancer therapeutic agent. This mAb is currently in Phase I clinical safety trials. Here we have evaluated the ability of this mAb to activate the TRAIL-R2 signaling cascade and assessed the in vitro and in vivo efficacy of HGS-TR2J in human tumor cell lines alone or in combination with various chemotherapeutic agents. Tumor cell lines were evaluated for TRAIL-R expression by flow cytometry and sensitivity to HGS-TR2J and chemotherapeutic agents in vitro. Human tumor cell lines from different tumor types expressed TRAIL-R2 on the cell surface and displayed moderate to significant sensitivity (50-90% cell death) to HGS-TR2J in vitro. In several different human tumor cell lines, HGS-TR2J enhanced the cytotoxic activity of chemotherapeutic agents. Importantly, some combinations elicited a synergistic effect on cell viability. Pre-established NSCLC and colon adenocarcinoma xenografts rapidly regressed after treatment with HGS-TR2J. Tumor volume was significantly reduced (90-75%) after the first dose of HGS-TR2J. The inhibition of tumor growth persisted throughout the duration of treatment and generated complete elimination of tumor in several animals. The rapid decrease in tumor volume was associated with a concomitant increase in the number of apoptotic cells in the tumor and an increase in levels of active caspases, an indicator of TRAIL-R pathway activity. In addition, there appeared to be fluctuations in TRAIL-R2 expression in xenografts as determined by immunohistochemistry. In summary, these data reveal HGS-TR2J has significant anti-tumor activity, alone and in combination with various chemotherapeutic agents, in an array of human tumor cell lines. This anti-tumor activity induces a concomitant increase in active caspases, an indicator of TRAIL-R pathway activity and apoptosis. Sensitivity to this TRAIL-R specific mAb extends beyond the requirement for cell surface receptor expression. These studies illuminate the potential of HGS-TR2J as a therapeutic for the treatment of human cancer.
Reduction in prescribing cannot confidently be attributed to scheme
Authors: E. Robinson, I. Harvey
Journal: BMJ (1996)

different, probably because of the way the schemes were applied.It is difficult to know how many of the practices participated actively in the Northern region's scheme because entry to the scheme was automatic; the uptake in Lothian was 75%.Table 1 shows the proportion of prac- tices in both regions that achieved their financial target and the proportions in Lothian that achieved the target for generic prescribing and the quality target.The quality target produced 33 audits of prescribing and 12 quality standards for prescribing at practice level.The disadvantage of applying Lothian's scheme is that it is time consuming for both practices and prescribing advisers, but the results suggest that tailoring a scheme to individual practices is an effective strategy.
Chloramphenicol promotes abnormal cell differentiation and inhibits apoptosis: A potential link to leukemia
Authors: Zeng-Rong Yuan, Yufang Shi
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1537 

Chloramphenicol is a broad-spectrum antibiotic and has been used to effectively control various infectious diseases worldwide. However, the development of leukemia following chloramphenicol administration is a serious side-effect in clinical medicine. The mechanisms underlining this leukemogenesis process have not been defined. In this study, we investigated the effect of chloramphenicol on activation of both human and mouse T cells. By stimulated mouse splenocytes and human peripheral mononuclearcytes with staphylococcal enterotoxin B in the presence of chloramphenicol, we found that chloramphenicol could induce these cells to undergo very abnormal differentiation characterized by very large size and multiploid nuclei. These cells express early T cell marker CD7, a phenotypic change may represent a differentiation process towards leukemogenesis. Interestingly, chloramphenicol also significantly inhibits activation-induced cell death observed in mouse lymphoblastic cells and several other human and mouse T cell lines. Blocking Fas ligand expression on surface of activated T cells is molecular mechanism for chloramphenicol inhibition in cell apoptosis. Since apoptosis plays a critical role for cellular homeostasis during tumorigenesis and immune response, our findings may potentially demonstrate a leukemogenesis mechanism associated with the application of chloramphenicol in clinic.
Case Histories in Psychosomatic Medicine
Authors: Winfred Overholser
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
Chemoprevention of MNU-induced mammary tumorigenesis in SD-rats by 1SY16 isolated from Agaricus blazei Murill K
Authors: Insu P. Lee
Journal: Cancer Research (2005)

4277   Previously, we have demonstrated that a low molecular fraction 1SY16 (∼500 dalton) isolated from  Agaricus blazei Murill K was found to be a very effective chemopreventive agent against NNK-, urethane or AOM-induced pulmonary adenoma, or colon ACF and colon carcinoma. Furthermore, chemopreventive effects of 1SY16 was closely associated with inhibition of cell cycle gene during the tumorigenesis. Present study was undertaken to evaluate whether chemopreventive effects of 1SY16 can be also demon-strated in MNU-induced mammary tumorigenesis. For the 1SY16 dose responsive effects were determined by treating 4 experimental groups, consisted of control, experimental group each receiving a single daily dose of 100, 200, or 400 mg 1SY16/kg bw for 15 days, immediately following a single administration of MNU via tail vein. To determine the stage specific chemopreventive effects of 1SY16 during the course of MNU-induced mammary tumorigenesis, 5 experimental groups, consisting of control, and 1SY16 treatment groups (200mg 1SY16/kg bw./day for the first, 2 nd , 3 rd , and 4 th  months after initiation. The results demonstrated that mammary tumor incidence in the 100, 200, or 400mg 1SY16/kg b.w./15 days groups were 22 (p 1  expression (90, 75, and 58% of control) and PCNA expression (92,73, and 68% of control) in mammary tumors. Chemopreventive effects of 1SY16 at different stages of tumorigenesis were 60 (p
Abstract 3393: Expression Patterns of the Cardiac Myofilament Proteins- Analysis of Surgical Myectomy Tissue from Patients with Sarcomeric Hypertrophic Cardiomyopathy
Authors: Jeanne L Theis, J. Martijn Bos, Bernard J Gersh, Steve R Ommen, Michael J Ackerman
Journal: Circulation (2007)

Background: Mutations in sarcomeric/myofilament proteins are commonly implicated in hypertrophic cardiomyopathy (HCM). However, the mechanisms underlying disease pathogenesis are not completely understood. Utilizing flash-frozen surgically resected left ventricular (LV) tissue from patients with obstructive HCM, we investigated the effect of sarcomeric HCM on tissue expression of various myofilament proteins. Methods: Frozen surgical specimens from 47 patients with HCM who underwent septal myectomy at the Mayo Clinic between 1999 and 2003 were examined. Using PCR, DHPLC, and direct DNA sequencing, all were genotyped for mutations involving the 8 myofilament-encoding genes that currently comprise the clinically available genetic test for sarcomeric HCM. Whole protein lysate was extracted from the frozen myectomy tissues and levels of myosin binding protein C, myosin heavy chain, alpha actin and alpha actinin were analyzed by Western Blot; GAPDH was used as a loading control. Frozen LV tissue derived from normal hearts of accidental death victims served as a reference group. Results: Overall, 25/47 (53%) patients had sarcomeric HCM including 13 patients with myosin binding protein C (MYBPC3) mutations and 10 with mutations in the beta myosin heavy chain (MYH7). Compared to normal heart tissue, the expression of myosin heavy chain was up-regulated significantly regardless of the underlying disease-causing genotype (genotype positive = genotype negative). However, there was gene-specific upregulation of myosin binding protein C with marked increases detected in patients with MYH7-HCM. In contrast, normal levels of myosin binding protein C were seen in patients with either MYBPC3-HCM or genotype-negative HCM. Conclusions: This is the first study to examine the expression pattern of sarcomeric proteins in a large collection of flash frozen human HCM myectomy tissue. Up-regulated, genotype-specific cardiac tissue expression of myosin binding protein C among patients with MYH7 (beta myosin heavy chain)-HCM suggests a novel compensatory pathway underlying the development of cardiac hypertrophy for one of most common genetic subtypes of HCM.
Aseptic Meningitis Outbreak Associated With Echovirus 9 Among Recreational Vehicle Campers—Connecticut, 2003
Authors: D. Waite, P. Beckenhaupt, L. LoBianco, P. Mshar, A. Nepaul, K. Marshall, T. Brennan, J. L. Hadler, W. A. Nix, M. Pallansch, E. M. Begier
Journal: JAMA (2004)
Expression of endothelin receptors in the progression to aggressive phenotype of prostate adenocarcinoma
Authors: Geeta Godara, Grant W. Cannon, Glenn M. Cannon, Joel B. Nelson, Beth R. Pflug
Journal: Cancer Research (2004)

3003   Endothelin-1 (ET-1), a potent vasoconstrictor, acts as a mitogen and survival factor in prostate cancer cells and exerts its action via two receptor subtypes, ET A  and ET B . This study investigated ET receptor expression with increasing aggressive phenotype in the Dunning rat prostate cancer model and determined the effect of combination therapy  in vivo  using highly selective ET A  inhibitor (atrasentan) with paclitaxel (chemotherapeutic agent). The prostate cancer cell lines used in this study ranged in aggressiveness from nontumorigenic (G), to tumorigenic, nonmetastatic (AT-1), to highly tumorigenic and metastatic (MLL). Saturation and competitive binding assays were carried out on the Dunning cell lines using  125 [I]-ET-1 with ET A  and ET B  antagonists for the competitive binding. Endothelin receptor expression in the cell lines was comfirmed using RT-PCR. ET-1 secretion by the MLL, AT-1 and G cells was quantified using an ET-1 ELISA assay. Subcutaneous injection of MLL cells into the flanks of nude mice was carried out prior to 3 weeks treatment with (a) vehicle alone (b) atrasentan (c) paclitaxel and (d) paclitaxel+atrasentan. The effects of combination therapy were assessed by tumor volume measurements and analysis of lung metastases. Saturation binding studies were carried out and receptor density of MLL and AT-1 cells were 7-fold and 3-fold higher than G cells respectively. The B max  for each cell line was consistent with the receptor density (G=11.48, AT-1=40.0, MLL=130.7 fmol/mg) and indicated an increase in ET-1 binding with the aggressive phenotype. Competitive binding assays demonstrated ET A  expression and no apparent ET B  expression. RT-PCR confirmed ET A  mRNA expression in the cell lines while no ET B  expression was observed. Since prostate cancer cells are expressing the ET A  subtype, combination therapy using atrasentan and paclitaxel were used for  in vivo  experiments. Combination therapy using atrasentan+paclitaxel had a greater effect on reduction of tumor volume than paclitaxel or atrasentan alone in comparison with vehicle treated animals. No statistically significant effect on tumor cell metastasis was observed with any treatment. In conclusion, this study demonstrated that increased ET A  expression is associated with tumor aggressiveness. ET A  receptor antagonist combined with chemotherapeutic agents may be helpful in reducing tumor growth in advanced prostate carcinoma.
Abstract 19059: Thermodilution-derived Coronary Blood Flow Pattern Immediately After Coronary Intervention as a Predictor of Long-term Clinical Outcomes in Patients With ST-segment Elevation Myocardial Infarction
Authors: Masashi Fukunaga, Kenichi Fujii, Machiko Nishimura, Tetsuo Horimatsu, Ten Saita, Akinori Sumiyoshi, Hiroto Tamaru, Kojiro Miki, Takahiro Imanaka, Tohru Masuyama
Journal: Circulation (2014)

Background: We reported that coronary blood flow (CBF) can be evaluated by analyzing thermodilution curve that is measured with a single pressure sensor/thermistor-tipped guidewire in the cardiac catheterization laboratory during percutaneous coronary intervention (PCI). Bimodal shape of thermodilution curve was associated with microvascular damage and predictors of left ventricular functional recovery after ST-segment elevation myocardial infarction (STEMI). However it is unknown whether the bimodal shape of thermodilution curve predicts mortality and re-hospitalization for heart failure in long term period for patients experiencing STEMI. Methods: Between September 2009 and August 2012, 97 consecutive patients with a first STEMI were prospectively enrolled in this study. Using a pressure sensor/thermistor-tipped guidewire, CBF pattern was assessed from the thermodilution-curves after successful PCI at maximum hyperemia. CBF pattern was classified into 3 groups according to the shape of thermodilution curve: a narrow unimodal (a rapid fall and rise of temperature-time curves) (n=47), a wide unimodal (a gradual fall and rise of temperature-time curves) (n=33), or bimodal (two populations with valley deeper than 20% of peak temperature drop) (n=17). Major adverse cardiac events (MACE) were defined as cardiac death and/or heart failure re-hospitalization within this study period. Results: Median follow-up period was 2.4 years. Although patients in the narrow-unimodal group and the wide unimodal group had a significantly lower incidence of MACE, patients in bimodal group had a higher risk of MACE during this study period (71, 15, 21%, p&lt;0.001). Multivariate analysis revealed that bimodal shape of the thermodilution-curve was the only independent predictor of MACE after STEMI (hazard ratio, 8.38; 95% confidence interval, 2.13-33.00; P=0.0023). Conclusions: A bimodal shape of the thermodilution curve is associated with the poor long-term clinical outcomes. This easily assessable coronary flow pattern is useful in clinical risk stratification for STEMI patients in the cardiac catheterization laboratory immediately after PCI.
Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration
Authors: Caroline Sabin, Signe Westring Worm, Rainer Weber, Peter Reiss, Wafaa El-Sadr, François Dabis, Stéphane De Wit, Mathew M.G. Law, Antonella d'Arminio Monforte, Nina Friis-Møller, Ole Kirk, Christian Pradier, Ian Weller, Andrew N. Phillips, Jens D Lundgren
Journal: The Lancet (2008)
"Hedgehog Ringworm"
Authors: M. P. English, C. D. Evans, M. Hewitt, R. P. Warin
Journal: BMJ (1962)

ACC-IDENTAL HYPOTHERMIA MEDIBCALJOURNAL 149conditions are shown to differ in that dehydration is an important factor in the chronic state needing correction during reheating.The effects of slow and rapid reheating are compared in Case 2, and it is suggested that the rapid method, certainly the choice in acute hypothermia, is probably to be preferred in all cases of hypothermia uncomplicated by frost-bite.A rapid method of reheating, using a warm bath, is shown to be practical even in a small il-equipped fishing trawler, and if some similar device were fitted to sea-rescue craft many lives might be saved.Some aspects of heat production and heat loss in a Channel swimmer are discussed.
The Federal Regulation of Food Labeling
Authors: David A. Kessler
Journal: New England Journal of Medicine (1989)

SHOULD Kellogg advertise All-Bran cereal as helping to reduce the risk of cancer?1 Should federal requirements for labeling nutrients mandate the disclosure of the cholesterol, fatty acid, and fiber content on food packages? Do food-labeling regulations create incentives for manufacturers to develop and market new foods — for example, a product named "low-fat mayonnaise"? The Food and Drug Administration (FDA) currently faces a broad range of food-labeling issues with direct relevance to the health of the American public.Regulating the Information on Food LabelsThe laws that govern the labeling of food were written 50 years ago, when there was . . .
Alpha-B-crystallin: a novel protein associated with invasive glioma phenotype
Authors: Dorota Goplen, Jian Wang, Per Ø. Enger, Stig O. Bøe, Ole D. Lærum, Rolf Bjerkvig
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3516 

By xenotransplantation of human brain tumor biopsies in nude rats, a highly invasive non-angiogenic phenotype, that express neural stem cell markers, was established. Serial animal passages led to less invasive, angiogenesis dependent tumors. Thus, human brain tumors can be modulated in vivo to provide a system for the predominantly invasive vs the angiogenic phenotype. We studied differential protein expression between the invasive and angiogenic glioma phenotype and used peptide mass fingerprinting and bioinformatics to identify differentially expressed proteins. By MALDI-TOF analysis we identified several over-expressed proteins in the most invasive glioma phenotype. One of the identified proteins was alpha-B-crystallin. Expression of alpha-B-crystallin in situ was verified by immunohistochemistry, where only the invasive glioma cells were stained. Immunohistochemistry of human GBM biopsies showed alpha-B-crystallin positive cells in the invasive tumor rim. This protein is also expressed by several human and rat glioma cell lines: U373, U251 and D54. Its expression in the invasive glioma phenotype and cell lines was confirmed by Western blots. To evaluate the role of alpha-B-crystallin in glioma cell migration in vitro, we applied siRNA on migrating glioma cells. Three days after transfection with alpha-B-crystallin siRNA, the migration distance was limited, and this effect lasted for several days. Moreover, immunohistochemistry revealed alpha-B-crystallin to be strongly and exclusively expressed in human glioblastomas as compared to normal brain. In the developing rat fetus alpha-B-crystallin was mainly expressed in the lens and developing heart. Alpha-B-crystallin is a small heat shock protein of 175 amino acids. It has autokinase activity and inhibits apoptosis. It has been reported that alpha-B-crystallin gene is overexpressed in BCNU resistant glioma cells. Here we demonstrate that alpha-B-crystallin is associated with highly invasive glioma phenotype, and inhibition of alpha-B-crystallin synthesis reduces glioma migration in vitro .
Structure-based design of AP23573, a phosphorus-containing analog of rapamycin for anti-tumor therapy.
Authors: Chester A. Metcalf, Regine Bohacek, Leonard W. Rozamus, Kimberley D. Burns, Jonathan B. Roses, Victor M. Rivera, Hao Tang, Jeffrey A. Keats, David C. Dalgarno, Joseph Snodgrass, David L. Berstein, Manfred Weigele, Tim Clackson
Journal: Cancer Research (2004)

2476  The mTOR protein, a PI3K-like kinase that links mitogenic stimuli and nutrient status to cell cycle progression, has emerged as an important target for anti-tumor therapy. Rapamycin is a natural product mTOR inhibitor that functions by inducing an inhibitory complex between the protein and cytoplasmic FKBP. The compound potently inhibits the proliferation of a wide variety of human tumor cell lines. We have used structure-based drug design to guide the synthesis of analogs of rapamycin that have optimal pharmacological properties for anti-tumor use. Computational modeling studies and previous SAR analyses indicated the possibility of replacing the C-43 secondary alcohol moiety of the cyclohexyl group of rapamycin with substituted phosphonate and phosphinate groups with retention of high-affinity binding to FKBP and mTOR. In particular, modeling indicated the existence of multiple surface residues with the potential to form favorable binding interactions with such C-43 substituents. In this study, we synthesized and evaluated a series of phosphorus-containing C43-modified rapamycin analogs. Semi-synthesis of the compounds from rapamycin using either one- or two-step conversions proceeded with high yield (>80%). Compounds were tested for FKBP binding affinity using a fluorescence polarization assay, and for the ability to inhibit the proliferation of human tumor-derived cell lines. Most of the compounds were found to have minimal reductions (less than 3-fold) in FKBP binding affinity, as predicted. In addition, the compounds inhibited the proliferation of the human fibrosarcoma cell line HT1080 with IC50 values of 0.1 –3 nM. Several of the compounds were equipotent to rapamycin in this assay (IC50 = 0.1 nM). Full details of structures and structure-activity relationships will be presented. AP23573, one of the most potent compounds, was selected for further study and development. The C43 modification of AP23573 was found to be stable in organic solvents, aqueous solutions at a variety of pHs, and in plasma and whole blood, both in vitro and in vivo. These stability studies along with in vitro metabolism studies also indicated that AP23573 is not a rapamycin pro-drug for rapamycin. AP23573 has shown potent inhibition of diverse human tumor cells lines in vitro and as xenografts implanted into nude mice. The compound is now being evaluated in phase 1 clinical trials in cancer patients.