tbuckley/cabot-search huggingface dataset:
Abstract 1621: Discovery of pyridyl pyrrolopyridinones as potent and selective CK1γ inhibitors
Authors: Hongbing Huang, Lisa Acquaviva, Howard Bregman, John Buchanan, Nagasree Chakka, Erin F. DiMauro, Jennifer Dovey, Hakan Gunaydin, Zihao Hua, Xin Huang, Liyue Huang, Vinod F. Patel, Matthew W. Martin, Randy Serafino, Cindy Wilson
Journal: Cancer Research (2014)

Abstract The canonical Wnt pathway regulates the ability of β-catenin to activate specific target genes. Aberrant activation of the Wnt pathway is believed to drive the development and growth of many cancers; for example, APC mutations were observed in &amp;gt;80% of the sporadic colorectal cancers. The casein kinase 1 (CK1) family of serine/threonine protein kinases is highly conserved. Multiple members of the CK1 family are shown to regulate the Wnt pathway through interactions with various proteins. The central role of CK1γ in Wnt signal transduction makes it an attractive target for the treatment of Wnt-pathway dependent cancers. We employed a structure-based approach and identified a series of pyridyl pyrrolopyridinones as potent and selective CK1γ inhibitors. These compounds exhibited good enzyme and cell potency, as well as selectivity against other CK1 isoforms, and favorable rodent PK profiles. Oral dosing of optimized lead compounds resulted in significant inhibition of LRP6 phosphorylation in a mouse tumor PD model. Citation Format: Hongbing Huang, Lisa Acquaviva, Howard Bregman, John Buchanan, Nagasree Chakka, Erin F. DiMauro, Jennifer Dovey, Hakan Gunaydin, Zihao Hua, Xin Huang, Liyue Huang, Vinod F. Patel, Matthew W. Martin, Randy Serafino, Cindy Wilson. Discovery of pyridyl pyrrolopyridinones as potent and selective CK1γ inhibitors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1621. doi:10.1158/1538-7445.AM2014-1621
Contribution of Antiviral Immunity to Oncolysis by Newcastle Disease Virus in a Murine Lymphoma&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: Monroe D. Eaton, Jeana D. Levinthal, Anthony R. Scala
Journal: JNCI Journal of the National Cancer Institute (1967)

By the injection of small numbers of cells with a large excess of Newcastle disease virus (NOV), an oncolytic effect was demonstrated against an ascites lymphoma induced by the Gross virus. Inbred histocompatible C3H mice were used in several experiments. Preimmunization of mice with NDV increased the oncolytic effect of that virus. With influenza virus an irregular oncolytic effect-occurred, but preimmunization with influenza virus did not increase resistance to ascites lymphoma cells treated with NDV. Syngeneic mice survived repeated injections of large numbers of NDV-treated leukemic spleen cells, but immunization with such cells did not confer significant resistance to challenge with smaller numbers of leukemic cells injected without virus.
The medical management of patients with cystic fibrosis following heart-lung transplantation
Authors: BP Madden, K Kamalvand, CM Chan, A Khaghani, ME Hodson, M Yacoub
Journal: European Respiratory Journal (1993)

Transplantation for end-stage respiratory failure in cystic fibrosis (CF), with encouraging medium-term results, is now possible. This paper details the postoperative medical treatment required by these patients. The management of 79 patients who underwent heart-lung transplantation is described. Details of intensive care, postoperative care, long-term follow-up, and the problems specific for cystic fibrosis patients are reported. The duration of care in the Intensive Care Unit (ICU) was 1-93 days (median 5 days). Intubation was required for 7 h to 93 days (median 48 h), and 11 patients required haemodiafiltration. High doses of cyclosporin A (mean 22 mg.kg-1 q.d.) were required. Acute rejection was common. There were 133 episodes of infection: bacterial 115, viral 11, and other organisms 7. Grand mal seizures occurred in 10 patients, lymphoproliferative disorders in 4, and obliterative bronchiolitis in 17. The median duration of hospital stay was 32 days. Despite having a multi-system disease, patients with CF can be successfully transplanted, if detailed attention is paid to their complex medical management.
Determination of Enantiomeric Homogeneity (Optical Purity) of Cyclophosphamide by Nuclear Magnetic Resonance Spectroscopy 2
Authors: Gerald Zan, Joan A. Brandt, William Egan
Journal: JNCI Journal of the National Cancer Institute (1977)

The enantiomeric homogeneity of resolved samples of the chiral anticancer drug cyclophosphamide was evaluated directly by 1H and 31P nuclear magnetic resonance spectroscopy with the use of the optically active shift reagent tris-[3-(trifluoromethylhydroxymethylene)-d-camphorato]europium(III). These measurements, in concert with optical rotatory dispersion spectroscopy, established that, for optically pure cyclophosphamide, |αD|=2.3±0.2°.
Carboplatin (NSC-241-240): an active platinum analog for the treatment of squamous-cell carcinoma of the head and neck.
Authors: M Eisenberger, J Hornedo, H Silva, R Donehower, M Spaulding, D Van Echo
Journal: Journal of Clinical Oncology (1986)

Carboplatin (CBDCA, Bristol-Meyers, New York) is a second generation platinum analog. Preclinical and phase I clinical studies have indicated a different spectrum of toxicity compared with the parent compound. In order to study the activity of carboplatin against cancer of the head and neck, 31 patients with recurrent or metastatic disease (30 squamous-cell and one adenoid cystic carcinoma) were treated with doses of 60 to 80 mg/m2 administered daily by intravenous (IV) bolus injections for five days, repeated at every 4- to 5-week intervals. In most cases, treatment was administered on an outpatient basis. Eight patients (26%; 95% confidence interval, 12% to 45%) had complete (CR) or partial responses (PR) with a median duration of 4.5 months. Moderate bone marrow suppression was the main toxicity. Mild nausea and vomiting was unusual and no neuro- or nephrotoxicity were seen. These preliminary data suggest that carboplatin has activity against advanced squamous-cell carcinoma of the head and neck comparable with the results reported with cisplatin alone in similar patient populations. The potential advantages over the parent compound relate to the absence of nephrotoxic effects and mild gastrointestinal toxicity which allows for outpatient treatment. Because carboplatin toxicity is directly dependent on its mechanism of renal excretion, particular attention should be given for its use in patients with impaired renal function or when combined with nephrotoxic agents. Similarly, because the dose limiting toxicity with this agent is primarily hematologic, its use in combination with other myelotoxic agents should be carefully undertaken. Further studies are indicated in order to define the spectrum of activity of the new generation platinum analogs in various tumors in humans.
Epidemiologic and clinicopathologic analysis of malignant mesothelioma for last 10 years in Korea
Authors: Soon-Hee Jung, Minseob Eom, Hyoung-Ryoul Kim, Sang-Baek Koh, Suk-Joong Yong, Myoung Ja Chung, Chang Hun Lee, Kwang-Sun Suh, Ji Sun Song
Journal: European Respiratory Journal (2011)

This study estimated the magnitude of malignant mesothelioma (MM) in Korea and its clinicopathologic features. We collected 479 cases through the Korea malignant mesothelioma surveillance system (KMMS) from 2001 to 2010. Using the clinical information, epidemiologic survey and pathological evaluations, the patients' age, sex, occupation history, tumor sites, specimen type, and histopathologic subtype were analyzed. Patients were 323 men (67%) and 156 women (33%). The average age was 60 years. The incidence of MM cases through KMMS was 0.79 per million. Among 152 cases with available occupational history, 56 (37%) were related with asbestos exposure occupation. The distribution of sites was pleura (72%), peritoneum (26%), and pericardium (2%). 67 patients were received a radical operation and others were diagnosed by ohter pathologic examination. The pathologic subtypes were epithelioid (62%), biphasic (12%), sarcomatoid (9%), and desmoplastic (3%) in order. We could estimate the accuracy rate (68%) of reporting cases of MM after comparing the data of Health Insurance Institute with the pathologic review of those cases in the university hospital. According to this rate, about 100 cases of MM could be occurred every year in Korea. The number of MM patients and the relation rate with occupational asbestos exposure were relatively low. The peak time of asbestos usage in Korea was 1995, so the incidence of MM is expected to increase continuously by 2030s. The KMMS supplemented by an active surveillance system using death certificate data, cancer registry data, and central surveillance system by the government support could be helpful to understand the more exact status of MM of Korea.
Lesson of the Week: The mineralocorticoid effects of high dose hydrocortisone
Authors: B H Ramsahoye, S V Davies, N El-Gaylani, D Sandeman, M F Scanlon
Journal: BMJ (1995)

Intravenous hydrocortisone in high doses is often prescribed when immunosuppression is required urgently, such as in the treatment of acute asthma.It is also sometimes used when patients are unable to take oral prednisolone.This practice is potentially dangerous, however, as high dose hydrocortisone may precipitate clinically significant hypokalaemia in susceptible patients.The importance of this effect is emphasised by the following report.
Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study.
Authors: A J Wozniak, J J Crowley, S P Balcerzak, G R Weiss, C H Spiridonidis, L H Baker, K S Albain, K Kelly, S A Taylor, D R Gandara, R B Livingston
Journal: Journal of Clinical Oncology (1998)

PURPOSE Cisplatin has played a major role in the treatment of non-small-cell lung cancer (NSCLC). This randomized trial was performed by the Southwest Oncology Group (SWOG) to determine whether the combination of vinorelbine and cisplatin has any advantage with regard to response rate, survival, and time to treatment failure over single-agent cisplatin in the treatment of patients with advanced NSCLC. METHODS Between October 1993 and April 1995, 432 patients with advanced stage NSCLC were randomized to receive arm I (cisplatin 100 mg/m2 every 4 weeks) or arm II (cisplatin 100 mg/m2 every 4 weeks and vinorelbine 25 mg/m2 weekly). All patients were chemotherapy-naive, had performance status (PS) 0 or 1, and had adequate hematologic, renal, and hepatic function. RESULTS Four hundred fifteen patients were eligible and assessable. On arm I (cisplatin), there was a 12% partial response rate. Arm II (cisplatin and vinorelbine) had a 26% response rate (2% complete responses and 24% partial responses, P = .0002). There was a statistically significant advantage with regard to progression-free survival (median, 2 v 4 months; P = .0001) and overall survival (median, 6 v 8 months; P = .0018) for the cisplatin and vinorelbine arm. One-year survival was 20% for cisplatin alone and 36% for the combination arm. There was more hematologic toxicity on arm II of the study (81% grades 3 and 4 granulocytopenia v 5% on arm I). Other toxicities, such as renal insufficiency, ototoxicity, and nausea and vomiting, and neuropathy were similar. CONCLUSION The results of this study indicate that the combination of cisplatin and vinorelbine is a superior treatment when compared with single-agent cisplatin in the treatment of advanced NSCLC. Cisplatin and vinorelbine is the new standard for SWOG against which new therapies will be evaluated.
Multiple Forms of Alpha-Galactosidase of the Mouse and Their Use as a Cell Marker in Tumorigenesis2
Authors: Jack E. Tobler, K. Bruce Jacobson
Journal: JNCI Journal of the National Cancer Institute (1978)

α-Galactosidase was examined as a possible biochemical marker for study of cellular kinetics of tumorigenesis In the mouse [(101 × C3Hf)F1 × (C57BL/6RL × SEC/RL)F1]. Enzyme activity was present in all tissues examined and was maintained in high, constant amounts in adult tissues. Multiple forms of α-galactosidase were isolated, one set by preparative gel electrophoresis and another by ion exchange chromatography. The two electrophoretic forms (the faster and the slower) compared with respect to their pH optima, Km (Michaelis constant), heat stabilities, and Inhibitor sensitivities were found to be indistinguishable by these characteristics. Inasmuch as neuraminidase treatment removed the electrophoretic difference, these two forms probably represented posttranscriptional modifications of the main form of α-galactosidase. DEAE-cellulose (DE-52) chromatography, however, resolved at least two major forms (peak I and peak II) that were independent of the electrophoretic forms. Peak I was unstable to electrophoresis and sensitive to pH changes and heat, had a high Km for the artificial substrate 4-methylumbelliferyl- α-d-galactoside, and was different from peak II by these criteria. Gel filtration experiments indicated that peak I could exist as proteins of 29,000 and 52,000 molecular weights, whereas peak II was observed to have a molecular weight of 125,000. Attempts to interconvert the two chromatographic forms failed. Possibly, peaks I and II are unrelated structurally and represent two different enzymes.
Neutrophil count trends in BAL samples from children being investigated for chronic cough
Authors: Vanessa Algar, Grace Choi, Konstantinos Douros, Mark Everard
Journal: European Respiratory Journal (2012)

Introduction : Investigating probable persistent bacterial bronchitis (PBB) with a bronchoscopy allows the identification of infectious agents and quantification of cellular responses in the paediatric population who rarely expectorate sputum under the age of 10.  Methods : Bronchoscopies in children carried out 2010-11 were identified and a retrospective case notes analysis done to identify those performed because of chronic cough or proven/probable PBB. Bronchoalveolar lavage (BAL) samples were analysed for standard bacterial culture, viral PCR and neutrophil count (%).  Results : 70 bronchoscopy BALs were analysed: 18.6% positive for bacterial and viral culture (B pos/V pos); 35.7% positive for bacteria but negative for viruses (B pos/V neg); 21.4% negative for bacteria but positive for viruses (B neg/V pos); 24.3% negative for both (B neg/V neg). Analysis of the BAL neutrophil count (%) was performed with one-way ANOVA and Cuzick9s test for trend. For the reasons of analysis the 4 groups were ordered as follows: group 1: B pos/V pos• group 2: B pos/V neg• group 3: B neg/ V pos• group 4 B neg/Vneg. The 4 groups differ significantly (means±sd:45.7±30.7, 18.6±21.4, 20.4±22.9, 11.6±15.2, for groups 1, 2, 3, and 4, respectively, p=0.001). Furthermore, a significant trend was found across the 4 ordered groups (p=0.003).  Conclusion : The presence of bacteria and viruses is associated with a significantly more neutrophils and thus a greater degree of inflammation than that induced by bacteria alone and could explain why recurrent viral infections are a feature of PBB.
Effects of Age and Ethnicity on the Link Between <i>APOE ϵ4</i> and Alzheimer Disease—Reply
Authors: Lindsay A. Farrer, L. Adrienne Cupples, Richard H. Myers, Cornelia M. van Duijn, Richard Mayeux, Jonathan L. Haines, Walter A. Kukull, Bradley Hyman, Margaret A. Pericak-Vance, Neil Risch
Journal: JAMA (1998)

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
Reversal by Vitamin A Analogues (Retinoids) of Hyperplasia Induced by N-Methyl-N′-nitro-N-nitrosoguanidine in Mouse Prostate Organ Cultures2
Authors: Dharam P. Chopra, Lee J. Wilkoff
Journal: JNCI Journal of the National Cancer Institute (1977)

The antihyperplastic activity of β-retinoic acid (RA) and nine synthetic analogues (retinoids) was examined in organ cultures of mouse prostate made hyperplastic by treatment with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). After 8 or 10 days, when most explants developed hyperplasia, the carcinogen was withdrawn and explants were incubated in control medium and medium containing different concentrations of a retinoid. The antimitotic activity of retinoids was compared with that of RA. Different retinoids produced variable degrees of mitotic inhibition in the hyperplastic prostate epithelium. The methylketo cyclopentenyl and 1-methoxyethyl cyclopentenyl analogues of RAwere at least 50-fold more active than RA in reversing MNNG-induced hyperplasia. The trimethylmethoxyphenyl analogue of RA and retinyl methyl ether were significantly more active than RA. Three analogues, N-acetylretinylamine, retinal acetyl hydrazone, and retinal oxime, were as active as RA. The chlorotrimethylphenyl analogue showed less activity than RA, and α-retinyl acetate was completely devoid of mitotic inhibitory activity.
Intracellular Distribution of Enzymes. VIII. The Distribution of Diphosphopyridine Nucleotide—Cytochrome C Reductase in Normal Mouse Liver and Mouse Hepatoma
Authors: George H. Hogeboom, Walter C. Schneider
Journal: JNCI Journal of the National Cancer Institute (1950)

Journal Article Intracellular Distribution of Enzymes. VIII. The Distribution of Diphosphopyridine Nucleotide—Cytochrome C Reductase in Normal Mouse Liver and Mouse Hepatoma Get access George H. Hogeboom, George H. Hogeboom Search for other works by this author on: Oxford Academic PubMed Google Scholar Walter C. Schneider Walter C. Schneider National Cancer Institute, National Institutes of Health, Public Health Service, Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 4, February 1950, Pages 983–987, https://doi.org/10.1093/jnci/10.4.983 Published: 01 February 1950 Article history Received: 31 January 1950 Published: 01 February 1950
Heparin-binding protein (HBP/CAP37): A missing link in neutrophil-evoked alteration of vascular permeability
Authors: Narinder Gautam, A. Maria Olofsson, Heiko Herwald, Lars F. Iversen, Evy Lundgren-Åkerlund, Per Hedqvist, Karl-E. Arfors, Hans Flodgaard, Lennart Lindbom
Journal: Nature Medicine (2001)
Screening for alpha-1 antitrypsin deficiency in Germany - Update 2012
Authors: Timm Greulich, Andreas Klemmer, Susanne Schroth, Christoph Nell, Viktor Kotke, Stefan Wiedmann, Christian Herr, Claus Franz Vogelmeier, Robert Bals, Andreas Rembert Koczulla
Journal: European Respiratory Journal (2012)

Background:  Alpha-1 antitrypsin deficiency (AATD) is characterized by decreased serum levels of alpha-1 antitrypsin (AAT). The most common clinical manifestations are pulmonary emphysema and liver cirrhosis. Epidemiological estimates postulate around 8000 people in Germany with a severe AATD. Although current guidelines stress the importance of screening for AATD, the majority of patients remains undetected.  Aim:  To provide recent screening data from the German central laboratory for AATD in Marburg, Germany.  Methods:  From dried blood spot (DBS) samples we performed AAT measurements (for internal use only) and genotyping for S and Z alleles. When either of both tests was suggestive for AATD we went on to perform phenotyping by IEF. When phenotyping resulted in bands suggestive for rare deficiency alleles we conducted complete sequencing of the AAT gene.  Results:  In the period from August 2003 to February 2012 more than 50.000 test kits had been requested of which 13.010 kits have been returned. Of these, 75 were not evaluable, and 185 samples had already been submitted before. Our results are based on 12.750 analyzed samples.  In descending order of frequency, we have diagnosed the following phenotypes: PIMM (8577, 67.27%), PiMZ (2383, 18.69%), PiZZ (846, 6.64%), PIMS (637, 4.99%), PiSZ (192, 1.51%), PiSS (38, 0.29%). 140 samples were submitted to gene sequencing. Here we found 75 rare (R) genotypes (PiZR 59; PiMR 10; PiSR 4; PiRR 2).  Conclusion:  Almost a third (32.73%) of the submitted samples was found to represent at least a carrier status, and over 8% carried a genotype that is associated with a severe AATD. We conclude that screening is useful to detect AATD and should be expanded in Germany.
Intraperitoneal chemotherapy with high-dose cisplatin and cytosine arabinoside for refractory ovarian carcinoma and other malignancies principally involving the peritoneal cavity.
Authors: M Markman, S Cleary, W E Lucas, S B Howell
Journal: Journal of Clinical Oncology (1985)

Sixty-two patients with refractory ovarian carcinoma or other malignancies principally confined to the peritoneal cavity were treated with an intraperitoneal combination chemotherapy regimen consisting of cisplatin (100 mg/m2 or 200 mg/m2) and cytosine arabinoside (4 X 10(-3) mol/L or 10(-2) mol/L). Sodium thiosulfate was simultaneously administered intravenously (IV) to protect against cisplatin-induced nephrotoxicity. Sixteen of 52 evaluable patients demonstrated evidence of a clinical response including 14 (36%) of 39 with refractory ovarian carcinoma. Systemic toxicity was not severe except for cisplatin-induced emesis and a single episode of major renal insufficiency. Dose-limiting toxicity was bone marrow suppression with cytosine arabinoside administered at 10(-2) mol/L. We conclude that combination intraperitoneal therapy with high-dose cisplatin and cytosine arbinoside can be safely administered with objective tumor responses observed in patients with ovarian carcinoma refractory to front-line chemotherapy and in occassional individuals with other malignancies principally confined to the peritoneal cavity.
Obstetrician is cleared of misconduct over baby’s death after attempted forceps delivery outside operating theatre
Authors: Clare Dyer
Journal: BMJ (2015)

A senior consultant obstetrician has been cleared of misconduct over her role in the delivery of a baby who died two days after an emergency caesarean.

A Medical Practitioners Tribunal Service panel found that Sharon Oates had made an “error of judgment,” which she admitted, in attempting a forceps delivery in the delivery room rather than taking the patient to the operating theatre.

Oates was also held to have used “inappropriate” language and to have caused distress in telling the parents after the baby was taken to the neonatal unit after the delivery, “Sorry about your baby. We didn’t anticipate it being as big as it was. It was never coming from that little bottom.”

But the panel cleared her of …