tbuckley/cabot-search huggingface dataset:
Abstract A18: Syndecan-1 is required for oncogenic Kras-driven PDAC tumorigenesis and maintenance
Authors: Wantong Yao, Wei Wang, Ayumu Taguchi, Avnish Kapoor, Amin Momin, Hong Jiang, Johnathon Rose, Muge Celiktas, Angela Deem, Samir Hanash, Ronald DePinho, Haoqiang Ying, Giulio Draetta
Journal: Cancer Research (2015)

Abstract Although the universal presence of KRAS mutations and their critical role in human pancreatic ductal adenocarcinoma (PDAC) designates it as an ideal therapeutic target, oncogenic KRAS (KRAS*) is still regarded as ‘undruggable’ to date. Therefore, to identify therapeutic points of intervention, it is critical to understand the impact of KRAS*-mediated pathways on in vivo tumor pathogenesis. We have recently generated an inducible KrasG12D-driven (iKRAS*) mouse PDAC model and established a critical role for sustained KRAS* activity in tumor maintenance, providing a model to characterize pathways required for KRAS*-dependent tumorigenicity. Cell surface proteins are relatively accessible and can provide candidates for biomarker discovery, as well as be utilized as therapeutic targets. To characterize the KRAS*-specific organization of cell surface proteins toward the development of possible diagnostic or therapeutic tools, we conducted an unbiased surfaceome analysis of tumor cells in the presence and absence of KRAS* signaling using the iKRAS* mouse PDAC model. Syndecans (SDC), a family of heparin sulfate proteoglycans, were identified as candidates whose membrane expression is correlated with KRAS* activity. Specifically, Syndecan-1 (SDC1) expression was upregulated in response to KRAS* induction in acinar-ductal metaplasia (ADM) and early pancreatic intraepithelial neoplasia (PanIN), but not in cerulein-induced chronic pancreatitis. Moreover, SDC1 membrane expression was abolished upon KRAS* extinction, and our data indicated that the MAPK pathway, but not the PI3K pathway, drives KRAS*-mediated SDC1 surface localization. Supportive of our findings, it has been shown that SDC1 expression is increased in premalignant and malignant pancreatic lesions of primary human PDAC, as well as in various other KRAS*-driven pancreatic cancer mouse models. To further study the role of SDC1 in KRAS*-driven pancreatic cancers, we generated an SDC1-knockout mouse model and crossed with LSL-KrasG12D-PDAC models. Our preliminary data indicate that genetic ablation of SDC1 expression effectively suppressed KRAS*-driven PDAC initiation and progression. The mechanisms of KRAS*-mediated SDC1 membrane localization and its impact on PDAC initiation and progression will be further explored. Citation Format: Wantong Yao, Wei Wang, Ayumu Taguchi, Avnish Kapoor, Amin Momin, Hong Jiang, Johnathon Rose, Muge Celiktas, Angela Deem, Samir Hanash, Ronald DePinho, Haoqiang Ying, Giulio Draetta. Syndecan-1 is required for oncogenic Kras-driven PDAC tumorigenesis and maintenance. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A18.
ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinases, blocks VEGF-C-induced activation of VEGFR-3 and cell proliferation in human colon cancer cell lines
Authors: T. Troiani, O. Lockerbie, M. Morrow, F. Ciardiello, S. G. Eckhardt
Journal: Journal of Clinical Oncology (2006)

13171 Background: Vascular endothelial growth factor receptors 1, 2 and 3 (VEGFR-1, -2 and -3) have a key role in activation and proliferation of endothelial cells, with expression of VEGFR-3 largely restricted to lymphatic endothelial cells. Although high expression of VEGFR-3 and its specific ligands, VEGF-C and VEGF-D, has been associated with an increased incidence of lymph node metastasis and a poor prognosis in different human malignancies, little is known about the role of this signaling pathway in tumor cells. This study investigated VEGFR-3 and its specific ligands in human colon cancer cells, and the antiproliferative activity of ZD6474, an inhibitor of VEGFR, epidermal growth factor receptor (EGFR) and RET tyrosine kinases, and of the EGFR inhibitors gefitinib and cetuximab. Methods: The expression of VEGFRs and EGFR was determined by RT-PCR, immunoblotting, flow cytometry and immunohistochemistry in four human colon cancer cell lines (HCT-116, HT-29, HCT-15 and SW480). Secretion of transforming growth factor-α (TGF-α), VEGF-A and VEGF-C by cancer cells was determined by ELISA. The in vitro antiproliferative effects of ZD6474, gefitinib and cetuximab were determined using an MTT assay. Results: All four human colon cancer cell lines expressed functional EGFR and secreted high levels of TGF-α. All four cell lines expressed VEGFR-1 and VEGFR-3, but not VEGFR-2, and secreted both VEGF-A and VEGF-C. Treatment with ZD6474 resulted in a dose-dependent cell growth inhibition (IC 50 3–5 μM), whereas treatment with gefitinib or with cetuximab produced little growth inhibition under the same culture conditions. Addition of VEGF-C induced a 2-fold increase in cell growth in vitro in all four colon cancer cell lines. Treatment with ZD6474 blocked both basal and VEGF-C-induced phosphorylation of VEGFR-3, as well as VEGF-C-induced cell proliferation. Conclusions: Human colon cancer cell lines express VEGFR-1 and VEGFR-3, and secrete VEGF-A and VEGF-C. A potential VEGF-C/VEGFR-3 autocrine loop has been identified in human colon cancer cells, which can be inhibited by ZD6474, suggesting that ZD6474 may have direct antitumor activity through inhibition of VEGFR signaling. [Table: see text]
Case 35-2000
Authors: Robert Udelsman, Henry Y. Dong
Journal: New England Journal of Medicine (2000)

Presentation of CaseAn 82-year-old woman was admitted to the ambulatory care center because of bilateral adrenal masses and low-grade fever.The patient had been in good health until five months earlier, when myalgia developed, with a vague headache and a temperature of 37.2°C. A physician prescribed ciprofloxacin because of scheduled cataract surgery. A week later, the patient began to pass three or more loose stools daily, without bleeding. A stool specimen contained Clostridium difficile toxin; another antibiotic was prescribed, and a repeated test for C. difficile toxin was negative. The diarrhea subsided. The cataract extraction was uneventful, and she . . .
A phase II breast cancer chemoprevention study of lovastatin in high-risk women: Initial feasibility data
Authors: A. W. Kurian, V. B. Sharma, E. J. Schwartz, M. A. Mills, A. D. Staton, N. M. Chun, K. E. Kingham, J. M. Ford
Journal: Journal of Clinical Oncology (2007)

1502 Background: More than 250,000 U.S. women have high inherited breast cancer risk; many develop hormone-receptor negative (ER/PR-) tumors, for which no chemoprevention exists. Pre-clinical data suggest that hydrophobic HMG-CoA reductase inhibitors (statins) may reduce risk of ER/PR- breast cancers. We report initial feasibility results of a phase II study of lovastatin for breast cancer chemoprevention. Methods: Study Design: Single-arm, non-randomized phase II study. Agent: Lovastatin 80 mg daily for 6 months. Primary Endpoint: Change in proportion of women with atypical cytology on 2-quadrant random periareolar fine needle aspiration (rpFNA) of breast duct cells before and after lovastatin. Secondary Endpoints: Changes in Ki-67, ER/PR, and elevated levels of oxidative DNA damage (ODD) measured by single-cell gel electrophoresis (Comet) assay of breast duct cells; changes in mammographic density; breast cancer incidence. Eligibility: BRCA1/2 mutation carrier, or estimated lifetime risk = 20% due to family history. Statistical Considerations: Planned sample size of 60, yielding 90% power to detect 50% change in proportion with atypia. Results: Twenty participants enrolled in Year 1; 15 have pre-study rpFNA and 5 have post-study rpFNA results to date. Pre-Study Cytology: N=15: 1 (7%, 95% confidence interval 0–32%) had insufficient, 11 (73%, 48–90%) had normal, and 3 (20%, 6–46%) had atypical cytology. Pre-Study Comet Assay: N=4 to date, 2 with atypical and 2 with normal pre-study cytology: 2 with atypical cytology (100%, 29–100%) had a positive Comet assay for elevated ODD, but 0 with normal cytology (0%, 0–71%) had a positive Comet assay. Post-Study Cytology: N=5, 1 with atypical cytology pre-study: 5 (100%, 51–100%) were normal post-study. Post-Study Comet Assay: N=1 to date, with atypical cytology and positive Comet assay pre-study: cytology was normal and Comet assay negative post-study. The study has been well-tolerated, with no drop-out. Conclusions: An early-stage chemoprevention study of lovastatin for 6 months, including 2 rpFNAs, appears feasible in high-risk women. Early results suggest a correlation between cytologic atypia and elevated levels of ODD, and the possibility that lovastatin might reverse these abnormalities. Accrual is ongoing. No significant financial relationships to disclose.
Predictors and correlates of adaptation to conjugal bereavement
Authors: M L Vachon, J Rogers, W A Lyall, W J Lancee, A R Sheldon, S J Freeman
Journal: American Journal of Psychiatry (1982)

The authors interviewed 162 widows 1, 6, 12, and 24 months after bereavement to determine which sociodemographic, prebereavement, and response variables and circumstances of the husband's death were related to distress level, as measured by the General Health Questionnaire (GHQ). The most important variable associated with high distress at 1 month was the woman's perception that she was seeing old friends less than before her husband's death. At 2 years it was possible to predict distress levels with 86% accuracy by means of a multiple regression analysis using 10 variables, including 1-month GHQ score, short final illness of the husband, and satisfaction with available help.
A phase I trial evaluating the safety and biological activity of iboctadekin (rhIL-18) in combination with rituximab in patients with CD20+ B-cell non-Hodgkin's lymphoma
Authors: M. J. Robertson, J. Kline, J. Bauman, O. Gardner, Z. Jonak, K. M. Koch, S. C. Murray, J. Weisenbach, J. Toso
Journal: Journal of Clinical Oncology (2009)

8566 Background: Iboctadekin (rhIL-18) is an immunostimulatory cytokine that has demonstrated anti-tumor activity in several preclinical models. When administered as monotherapy in phase I clinical studies, rhIL-18 was safe, well tolerated and induced potent biological responses (e.g. Th1 cytokine production and expression of activation markers on NK, CD8+ and CD4+ cells). These data affirm the endogenous role of IL-18 as a co-stimulatory cytokine and suggest that its optimal use would be in a combination with other immune modulators such as rituximab. Methods: Patients with CD20+ B cell non-Hodgkin's lymphoma are being given rituximab (375 mg/m2) IV weekly for 4 consecutive weeks in combination with ascending doses of intravenous rhIL-18 (1 to 100 mcg/kg in 6 cohorts of 3 patients each) IV weekly for 12 weeks to identify a dose that is safe and tolerable and gives a maximum biological effect. Eligible patients must have disease which progressed after standard therapy or for which there is no effective standard treatment. Assessments include safety/tolerability, pharmacokinetics, pharmacodynamics (serum cytokines, peripheral blood phenotypic markers and tumor biomarkers), immunogenicity and anti-tumor activity. Results: To date, thirteen subjects have been enrolled in the first four cohorts (1, 3, 10 and 20 mcg /kg of rhIL-18). The combination is well tolerated with a safety profile similar to that observed with rituximab or rhIL-18 monotherapy. The pharmacodynamic response is as expected with a dose-dependent decrease in circulating activated (CD69+) NK cells within 4 hours after completing the rhIL-18 infusion which rebound to pre-dose levels within 2–4 days. Using the International Working Group response criteria for lymphoma, two subjects had complete responses at 10 and 20 mcg/kg, one subject had a partial response at 10 mcg/kg and three subjects had stable disease at 1, 3 and 3 mcg/kg. Conclusions: These data show that the combination of rhIL-18 and rituximab is safe, well tolerated and induces potent biological activity. This study will define the dose level to be used in a future phase II trial evaluating this combination in patients with relapsed or refractory follicular lymphoma. [Table: see text]
Increased Plasma Protein Binding of Propranolol and Chlorpromazine Mediated by Disease-Induced Elevations of Plasma α<sub>1</sub>Acid Glycoprotein
Authors: Kenneth M. Piafsky, Olof Borgå, Ingegerd Odar-Cederlöf, Catja Johansson, Folke Sjöqvist
Journal: New England Journal of Medicine (1978)

To assess the importance of disease-induced increases in plasma concentrations of alpha1 acid glycoprotein (an acute-phase plasma protein that binds cationic drugs), we determined binding of propranolol in plasma from 53 patients and 25 healthy volunteers. Binding was increased in 10 patients with Crohn's disease (P less than 0.002), nine with inflammatory arthritis (P less than 0.002) and eight with chronic renal failure with superimposed inflammatory disease (P less than 0.01) as compared with healthy controls. The plasma binding of control subjects did not differ from that of 12 patients with chronic hepatic disease (P greater than 0.45) or 14 with uncomplicated renal failure (P greater than 0.80). Chlorpromazine binding, determined in 60 subjects, yielded similar results. Percentage of free drug and alpha1 acid glycoprotein concentration were inversely correlated (r = -0.77 with propranolol, P less than 0.001, and r = -0.69 with chlorpromazine, P less than 0.001). Increases in plasma protein binding in patients with inflammatory disease appear mediated by increases in alpha1 acid glycoprotein concentration, which may influence drug kinetics.
Case 31-1999
Authors: Henry M. Greenberg, H. Thomas Aretz
Journal: New England Journal of Medicine (1999)

Presentation of CaseA 33-year-old man was admitted to the hospital because of wide-complex tachycardia.The patient had been well until the evening of admission, when he had a five-minute episode of palpitations accompanied by dyspnea, dizziness, and a rapid, irregular pulse. He came to the hospital, where an electrocardiogram showed several episodes of wide-complex tachycardia at a rate of 150 to 190 beats per minute; each episode was associated with palpitations and dizziness. Lidocaine was administered intravenously, and no additional episodes occurred.The patient had a history of hypertriglyceridemia, with recorded triglyceride levels of up to 1203 mg per . . .
Rhinocerebral Mucormycosis
Journal: JAMA (1963)

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 Treatment of Unrelated Disorders in Patients with Chronic Medical Diseases
Authors: Donald A. Redelmeier, Siew H. Tan, Gillian L. Booth
Journal: New England Journal of Medicine (1998)

Patients can have several illnesses concurrently, yet some of these diseases may be neglected if one problem consumes attention. We conducted a population-based analysis in Ontario, Canada — where universal health insurance is provided — to determine whether unrelated disorders are less likely to be treated in patients with chronic diseases.
P181 Indwelling pleural catheters for malignant pleural effusions – do septations change outcomes?
Authors: E Nuttall, H Balata, M Al-Aloul, M Evison, J Holme
Journal: Thorax (2015)

<h3>Introduction</h3> The insertion of indwelling pleural catheters (IPCs) allows outpatient based management of pleural effusions and has been shown to be effective as a primary management strategy and following failed attempts at pleurodesis. The presence of septations may be associated with incomplete drainage and may make the procedure more complex. This study aimed to assess if the presence of septations on thoracic ultrasound changed the outcome of IPC insertion and to review complication rates. <h3>Method</h3> Prospective data is collected for patients undergoing insertion of IPCs at a tertiary pleural referral centre. Pre-procedure thoracic ultrasound is performed in all patients and a grading of septations made; no septations, mild (&lt;4), moderate (4–9), severe septations (&gt;9). Immediate, early (30 days) complications as well as six month follow-up data are recorded. This study is a retrospective analysis of this prospectively maintained database. <h3>Results</h3> A total of 47 patients with complete datasets were identified between 2013–2014; 34% (16/47) had mild/moderate/severe septations (n = 7, 5, 4 respectively) and 66% (31/47) had no septations. There was no significant difference in the number of patients achieving resolution of pleural effusion and pleurodesis whereby the IPC could be removed according to the presence of septations (pleurodesis in those with no septations 16%, 5/31 vs. 13%, 2/16 in those with septations, p = 1.0). There were no patients in either group in whom the drain was removed due lack of drainage in the context of a persistent pleural collection. There was no significant difference in overall complication rate according to the presence of septations (16%, 5/31, in the no septation group vs 13%, 2/16, in the septation group, p = 1.0). <h3>Conclusion</h3> These results suggest that the presence of septations on the pre-insertion thoracic ultrasound do not affect the rate of pleurodesis or drain removal due to lack of drainage and persistent pleural effusion. The numbers in the study are small and a limitation is the lack of assessment of post-procedure breathlessness in our patients (e.g. with a visual analogue scale). The presence of septations should not deter consideration of IPC insertion in the management of malignant pleural effusions.
Importance of the Lay Press in the Transmission of Medical Knowledge to the Scientific Community
Authors: D P Phillips, E J Kanter, B Bednarczyk, P L Tastad
Journal: New England Journal of Medicine (1991)

Efficient, undistorted communication of the results of medical research is important to physicians, the scientific community, and the public. Information that first appears in the scientific literature is frequently retransmitted in the popular press. Does popular coverage of medical research in turn amplify the effects of that research on the scientific community?To test the hypothesis that researchers are more likely to cite papers that have been publicized in the popular press, we compared the number of references in the Science Citation Index to articles in the New England Journal of Medicine that were covered by The New York Times with the number of references to similar articles that were not covered by the Times. We also performed the comparison during a three-month period when the Times was on strike but continued to prepare an "edition of record" that was not distributed; doing so enabled us to address the possibility that coverage in the Times was simply a marker of the most important articles, which would therefore be cited more frequently, even without coverage in the popular press.Articles in the Journal that were covered by the Times received a disproportionate number of scientific citations in each of the 10 years after the Journal articles appeared. The effect was strongest in the first year after publication, when Journal articles publicized by the Times received 72.8 percent more scientific citations than control articles. This effect was not present for articles published during the strike; articles covered by the Times during this period were no more likely to be cited than those not covered.Coverage of medical research in the popular press amplifies the transmission of medical information from the scientific literature to the research community.
Treatment of Cyclic Neutropenia with Granulocyte Colony-Stimulating Factor
Authors: William P. Hammond, Thomas H. Price, Lawrence M. Souza, David C. Dale
Journal: New England Journal of Medicine (1989)

Six patients with cyclic neutropenia were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) for 3 to 15 months. All had a history of recurrent aphthous stomatitis, pharyngitis, lymphadenopathy, fever, and numerous infections during periods of neutropenia. Serial blood-cell counts, findings on bone marrow examination, and signs and symptoms were evaluated before and during the daily administration of G-CSF (3 to 10 μg kilogram of body weight per day), either intravenously or subcutaneously. The kinetics of labeled autologous blood neutrophils and the migration of neutrophils to skin chambers were also measured. Recombinant human G-CSF increased the mean (±SEM) neutrophil counts from 717±171 per microliter to 9814±2198 per microliter (P = 0.009). In five of the six patients, the cycling of blood-cell counts continued, but the length of the period decreased from 21 to 14 days. The number of days of severe neutropenia was reduced (P = 0.002). Neutrophil turnover increased almost four-fold (P = 0.005), whereas neutrophil migration to a skin chamber was normal. G-CSF therapy reduced the frequency of oropharyngeal inflammation, fever, and infections in these patients. During the first 40 months of treatment, no typical mouth ulcers or bacterial infections occurred; recurrent gingivitis improved. We conclude that G-CSF is effective for the treatment of cyclic neutropenia in humans. (N Engl J Med 1989; 320:1306–11.)
Enhanced Local Production of Complement Components in the Small Intestines of Patients with Crohn's Disease
Authors: Örjan Ahrenstedt, Lars Knutson, Bo Nilsson, Kristina Nilsson-Ekdahl, Bo Odlind, Roger Hällgren
Journal: New England Journal of Medicine (1990)

There is evidence that complement components may be formed locally in inflammatory lesions containing monocytes and macrophages. To investigate the role of complement in Crohn's disease we measured jejunal-fluid concentrations of the complement components C4, C3, and factor B by perfusion of a closed segment of the jejunum in 22 patients with Crohn's disease thought to be limited to the terminal ileum.