tbuckley/cabot-search huggingface dataset:
Anti-leukemia activity of CD33-specific chimeric cytotoxic T lymphocytes in vitro and in vivo is impaired by addition of the CD28 costimulatory endodomain
Authors: A. Dutour, D. Lee, S. Napier, E. Yvon, H. Finney, M. Brenner, R. Rousseau
Journal: Journal of Clinical Oncology (2007)

3052 Background: EBV-specific cytotoxic T cells (EBV-CTLs) expand and have long-term activity in vivo due to the sustained costimulation provided by the EBV-infected cells produced by this persistent virus. We exploited this phenomenon and redirected EBV-CTLs against CD33, a surface protein expressed on the malignant blasts of acute myeloid leukemia (AML) cells. Methods: EBV-CTLs generated from six EBV-seropositive donors were transduced using a retroviral vector encoding CD33 specific chimeric receptor (cR). We evaluated whether the high and sustained activity shown against native EBV+ target cells can be extended to the CD33+ EBV- targets of the chimeric receptor and whether the addition of CD28 signaling domain improved the receptor activity. Results: cRCD33-EBV-CTL maintained killed EBV-LCL and CD33 + targets (specific lysis respectively of 30% and 35% at E:T ratio 25:1). They produced Th-1, Th-2 and Tc cytokines on exposure to CD33 + targets. Addition of the CD28 intracellular domain did not increase cytotoxicity to CD33 + targets. Preincubation of CD33 + cells with the CD33-blocking MoAb resulted in up to 40% inhibition of lysis and up to 60% inhibition of cytokine release by cRCD33-EBV-CTLs confirming the specificity of the TCR interactions with CD33. NOD-SCID mice bearing a human CD33 + AML were injected with EBV-CTLs ×4 weekly starting 5 days after tumor inoculation. Significant tumor reduction was only observed in mice treated with the cRCD33-EBV-CTLs (p&lt;0.05). Immunohistologic analysis showed the presence of a majority of CD8 + human T cells in the tumors of treated mice. Incorporation of the CD28 endodomain resulted in less tumor-infiltrating T cells in mice treated with cRCD33CD28-EBV-CTLs. There was no significant difference in the chemokines receptor expression on cRCD33CD28-EBV-CTLs but their rate of apoptosis was 16 % higher (p&lt;0.05) than the one of cRCD33-EBV-CTLs. Conclusions: EBV- CTL expressing the CD33 chimeric receptor are functional in vitro and in vivo in mice. CD28 signaling may have a deleterious role for the activity of chimeric receptors in vivo. No significant financial relationships to disclose.
Racial differences in acute toxicities of FEC 100 chemotherapy in patients with breast cancer
Authors: H. S. Han, I. Reis, K. Kuroi, M. Toi, E. Suzuki, R. Syme, L. Chow, A. Yip, W. Zhao, R. Nimmagadda, S. Gluck
Journal: Journal of Clinical Oncology (2009)

e11515 Background: Racial disparities in breast cancer outcomes are attributed to differences in baseline tumor characteristics, stage, and socioeconomic factors. However, little is known about racial differences in treatment-related toxicities. We hypothesized that racial and ethnic differences result in differential tolerance to chemotherapy and possibly compromise to the dose intensity of adjuvant/neoadjuvant chemotherapy. Methods: Data was collected from 4 international collaborating centers (University of Miami, JBCRG (Japan Breast Cancer Research Group), University of Hong Kong, and Tom Baker Cancer Center) at which patients of different ethnic background have been treated for non metastatic breast cancer with same adjuvant or neoadjuvant chemotherapy of FEC 100: fluorouracil 500 mg/m 2 , epirubicin 100 mg/m 2 , and cyclophosphamide 100 mg/m 2 ). Racial/ethnic differences in toxicities were assessed by first episode of grade 2 or higher toxicity. Analysis of data was performed at the University of Miami. Results: Treatment-related toxicities are compared according to four race/ethnicity groups (120 Caucasian from USA and Canada (C), 16 African American (AA) from USA and Canada, 141 Japanese Asian (JA), and 23 Asian from Hong Kong (HKA)) (Table). JA and HKA had a significant higher rate of grade 3 or higher toxicity compared with C or AA women; 65%, 61%, 28%, and 31% respectively. However, there were no significant differences in chemotherapy dose intensity or density across the 4 race/ethnicity groups. Conclusions: This unique study noted racial differences in acute toxicity in women with breast cancer who were treated with FEC 100 chemotherapy. However, there are several limitations including the retrospective nature of our study, differences in practice across four countries, and different number of patients available for comparison. This study is ongoing and further statistical analyses are planned when a larger sample size is reached. [Table: see text] No significant financial relationships to disclose.
Purification of Malignant Cells and Lymphocytes From a Rat Transplantable Mucinous Adenocarcinoma of the Colon by Isokinetic Sedimentation in Gradients of Ficoll 2
Authors: Theresa P. Pretlow, Gregory L. Glover, Thomas G. Pretlow
Journal: JNCI Journal of the National Cancer Institute (1977)

The Ward transplantable rat colon carcinoma was disaggregated with 0.25% trypsin in tissue culture medium, and the resulting suspension of cells was separated by sedimentation in linear gradients of Ficoll in tissue culture medium. Prior to separation, the suspension of tumor cells contained four types of morphologically different malignant cells (32.5%, type I; 8.2%, type II; 17.9%, type III; and 14.0%, type IV) in addition to 14.2% lymphocytes, 3.4% macrophages, 0.6% granulocytes, 1.9% unidentified mononucleated cells, and 7.5% red blood cells. After sedimentation for 14 minutes at 4° C in a previously described isokinetic gradient at a centrifugal force of 97xg, malignant cells comprised 97.0% of the nucleated cells in the purest gradient fractions; after isopyknic sedimentation for 30 minutes at a centrifugal force of 2,200xg, malignant cells comprised 98.7% of the nucleated cells in the purest gradient fractions. Lymphocytes constituted 90.4% of the nucleated cells in the purest gradient fraction after isokinetic sedimentation, but were not purified by isopyknic sedimentation. Fractions 11–23 of the isokinetic gradient contained 85–95% morphologically malignant cells. When these cells were injected into rats, tumors were evident within 10 weeks. Fractions 7–9 of the gradient contained mostly red blood cells and lymphocytes and less than 5% morphologically malignant cells. Cells from these fractions failed to produce tumors even 4 months after rats were inoculated with tenfold more cells than were needed to produce tumors from fractions 11–23.
Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma
Authors: Jessica Okosun, Rachel L Wolfson, Jun Wang, Shamzah Araf, Lucy Wilkins, Brian M Castellano, Leire Escudero-Ibarz, Ahad Fahad Al Seraihi, Julia Richter, Stephan H Bernhart, Alejo Efeyan, Sameena Iqbal, Janet Matthews, Andrew Clear, José Afonso Guerra-Assunção, Csaba Bödör, Hilmar Quentmeier, Christopher Mansbridge, Peter Johnson, Andrew Davies, Jonathan C Strefford, Graham Packham, Sharon Barrans, Andrew Jack, Ming-Qing Du, Maria Calaminici, T Andrew Lister, Rebecca Auer, Silvia Montoto, John G Gribben, Reiner Siebert, Claude Chelala, Roberto Zoncu, David M Sabatini, Jude Fitzgibbon
Journal: Nature Genetics (2015)
Discrimination Against People With Dermatologic Diseases
Authors: Adam S. Aldahan, Vidhi V. Shah, Stephanie Mlacker, Suzanne M. Aldahan, Keyvan Nouri
Journal: JAMA Dermatology (2016)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Phase I open-label study of cediranib plus etoposide (E) and cisplatin (P) as first-line therapy for patients (pts) with small cell lung cancer (SCLC) or lung neuroendocrine cancer (NEC).
Authors: J. Heymach, B. S. Glisson, R. C. Doebele, C. Huang, D. R. Gandara, S. Le Scouiller, M. A. Marotti, D. R. Camidge
Journal: Journal of Clinical Oncology (2010)

7050 Background: Cediranib is an oral, highly potent inhibitor of VEGF signaling with additional activity versus c- Kit. This study assessed cediranib plus EP as first-line therapy for extensive stage/metastatic lung cancer. Methods: Pts received up to six 21-day cycles of EP (E 100 mg/m2, days 1–3; P 80 mg/m2, day 1) with once-daily cediranib from day 4 of cycle 1 until disease progression or toxicity and were eligible for safety review if they completed the first 21 days of cediranib or had a dose limiting toxicity (DLT). The primary objective was assessment of safety and tolerability. If < 33% pts in a cohort experienced a DLT the dose was deemed tolerable and 12 additional pts recruited to an expanded cohort. Results: At data cut-off (Aug 09), 22 pts (50% male; mean age 60 years; SCLC/NEC histology 82%/18%; WHO PS 0/1/2 14%/77%/9%) had received treatment. Recruitment to the 30 mg cohort was stopped at 4 pts (all SCLC) when 20 mg became the recommended dose with chemotherapy. The following results relate to cediranib 20 mg + EP (n = 18, 14/4 SCLC/NEC). As only 1/6 pts in the initial 20 mg cohort experienced a DLT (hemoptysis), this combination was considered suitable for cohort expansion. Adverse events (AEs) reported in ≥ 50% pts receiving cediranib 20 mg + EP were nausea, vomiting, neutropenia and diarrhea. The incidences of hypertension (all G1 or 2) and fatigue (n = 1 G3) were both 39%. Five pts discontinued treatment due to an AE: anemia, duodenal ulcer bleeding, increased creatinine (all n = 1, G3) and hemoptysis (n = 2, G3). There were no cediranib dose reductions (mean daily dose 18.5 mg) and all pts received the planned dose of EP. In a preliminary efficacy assessment (RECIST), 10/14 (71%) SCLC pts achieved a partial response (PR) (12/18 [67%] including 30 mg cohort). In the 20 mg cohort, the mean best change from baseline in tumor size was -53.3%. Median PFS was 8 months and 5/8 ongoing pts had a PR. Conclusions: Cediranib 20 mg + EP is well tolerated and has shown evidence of activity in SCLC and lung NEC. Preliminary median PFS is favorable compared with EP historical data. The AE profile is consistent with previous cediranib studies. Further investigation is warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Response Genetics Amgen, AstraZeneca, Biodesix, Bristol-Myers Squibb/ImClone, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Lilly, Merck, Novartis, Pfizer, sanofi-aventis AstraZeneca AstraZeneca Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb/ImClone, Genentech, Lilly, Merck, Novartis, Pfizer
Preserved Levels Of Uninvolved Immunoglobulins Are Associated With Better Overall Survival In Patients With Multiple Myeloma Independently Of Disease Burden: A Role For The Immune System?
Authors: Meletios A. Dimopoulos, Argiris S. Symeonidis, Flora Zagouri, Anastasia Sioni, Anastasia Pouli, Sosana Delimpasi, Eirini Katodritou, Eurydiki Michalis, Michalis Michael, Eleftheria Hatzimichael, Amalia Vassou, Panagiotis Repousis, Anna Christoforidou, Zafiris Kartasis, Ekaterini Stefanoudaki, Catherine Megalakaki, Stavroula Giannouli, Marie-Christine Kyrtsonis, Kostas Konstantopoulos, Evangelos Terpos, Efstathios Kastritis
Journal: Blood (2013)
Secondary malignancy after treatment of Hodgkin's disease: an evolving picture.
Authors: C N Coleman
Journal: Journal of Clinical Oncology (1986)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1986.4.6.821 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3711957 Secondary malignancy after treatment of Hodgkin's disease: an evolving picture. C N ColemanxC N ColemanSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.6.821 First Page PDF © 1986 by American Society of Clinical Oncology
Transcriptional analysis of the human BPIFA1/SPLUNC1 gene
Authors: Ryan Taylor, Lynne Bingle, Colin Bingle
Journal: European Respiratory Journal (2013)

Despite being one of the most highly expressed genes in the respiratory tract nothing is known about the molecular basis of the cell type specific expression of the BPIFA1/SPLUNC1 gene. Though the gene is very highly expressed in differentiated tracheobronchial epithelial cells cultured at an air liquid interface these cells are refractory for traditional promoter analysis and only a limited number of cell lines express the gene robustly. We have shown that the adenosquamous carcinoma cell line, NCH H647 is one such cell and in the present study we have used this line to begin to characterize the proximal promoter of the human BPIFA1 gene. We performed a bioinformatic analysis to identify the likely proximal promoter and we generated a deletion series of reporter constructs in pGL3 corresponding to this region located within 1kb upstream of the transcription start site. Transfection of these constructs confirmed that these elements contained positive regulatory regions and we could show that this element resides within the first 300bp of the putative promoter region. Transfection of these constructs into a second expressing cell line (NCI H292) confirmed the localisation of this element. As we have previously shown that BPIFA1 expression is down regulated by treatment with interferon gamma (IFNg) we treated cells transfected with the constructs alongside others that had been transfected with the IFNg responsive promoter from the SCGB1A1/CCSP gene. These results suggest that BPIFA1/SPLUNC1 is repressed by an IFNg responsive element located in the proximal promoter. These proximal promoter elements will be essential for uncovering the molecular basis of the tissue specific expression of the BPIFA1/SPLUNC1 gene.
Abstract P105: Women with Atrial Fibrillation have Increased Risk of Incident Stroke: Insights from a Propensity-Matched Study of the AFFIRM Trial
Authors: Brita Roy, Ravi V Desai, Mustafa I Ahmed, Gregg C Fonarow, Wilbert S Anorow, Ali Ahmed
Journal: Circulation (2012)

Background: Women with atrial fibrillation (AF) have been reported to have poor outcomes. It remains unclear if this association is intrinsic or mediated by the higher comorbidity burden of female AF patients. Therefore, we examined the association between sex and outcomes in a balanced cohort of propensity-matched AF patients who participated in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial. Methods: Of the 4060 AFFIRM patients, 1594 (39%) were women. Propensity scores for female sex were calculated for each of the 4060 patients, and were used to assemble a cohort of 1097 pairs of men and women who were balanced on 51 baseline characteristics, including major cardiovascular (CV) risk factors and medication use, including warfarin. Matched Cox regression models were used to estimate the association between female sex and outcomes during 6 years of follow-up. Results: Patients (n=4060) had a mean (±SD) age of 70 (±8) years and 13% were African American. All-cause mortality occurred in 19% and 15% of matched men and women, respectively (matched HR when women were compared to men, 0.88; 95% CI, 0.69-1.11; p=0.279). All-cause hospitalization occurred in 61% of both men and women (matched HR for women, 1.06; 95% CI, 0.93-1.21; p=0.372). Sex was not associated with CV hospitalization (matched HR for women, 1.13; 95% CI, 0.97-1.32; p=0.111). Ischemic stroke occurred in 3% and 5% of matched men and women, respectively (OR when women were compared to men, 2.02; 95% CI, 1.28-3.18; p=0.002). There was no sex-related difference in major bleeding (7% each). Conclusion: In a cohort of AF patient in which men and women were well-balanced on 51 baseline characteristics including warfarin use, women had increased risk of stroke, but there was no sex-related variation in all-cause mortality or CV hospitalization.
Abstract 200: Hypercoagulabilty Panel Testing in Neonates Undergoing Cardiac Surgery
Authors: Sirisha Emani, David Zurakowski, Christopher Baird, Frank Pigula, Trenor Cameron, Sitaram M Emani
Journal: Circulation Research (2012)

Thrombosis is a crucial contributor of morbidity and mortality in neonates undergoing cardiac surgery. Although there is published data on several factors of the hemastatic system, there is no data correlating factor expression and/or function with thrombosis in neonates. We tested the hypothesis that hypercoagulability markers are predictive of thrombosis in neonates undergoing cardiac surgery. Sixty neonates undergoing cardiac surgery were tested for thrombin generation assay; coagulation factors; antithrombin III, protein C, protein S, and factor VIII; fibrinolytic inhibitors; thrombin-activatable fibrinolytic inhibitor, plasminogen activator inhibitor; and presence of cardiolipin antibodies by immunoassays. Factor V Leiden mutation was also tested in a few patients utilizing single nucleotide polymorphism assays. In this pilot study, thrombosis occurred in 15% of the neonates undergoing cardiac surgery. Significant risk factors associated with thrombosis were pre-mature birth, use of cardio pulmonary bypass, and single ventricle physiology. Hypercoagulability factors associated with thrombosis determined by univarent analysis were elevated thrombin generation, enhanced expression of thrombin-activatable fibrinolytic inhibitor and plasminogen activator inhibitor as well as presence of cardiolipin antibodies and factor V Leiden mutation. No correlation was observed between thrombosis and expression of coagulation factors antithrombin III, protein C, protein S, and factor VIII. Multivarient analysis has proven to show thrombin generation, thrombin-activatable fibrinolytic inhibitor, and presence of cardiolipin antibodies as multivariable predictors of thrombosis. These significant hypercoagulability markers are independent predictors of thrombosis. Thus thrombosis predictability can help in post-operative management and care for neonates undergoing cardiac surgery by regulating pro- and/or anti-coagulation therapy.
Differences of mutation of <i>helicobacter pylori</i> cagA gene isolated from duodenal ulcer and gastric cancer.
Authors: Sung Soo Kim, Dae Young Cheung, Soo-Heon Park
Journal: Journal of Clinical Oncology (2015)

69 Background: H. pylori is the pathogen of both duodenal ulcer and gastric carcinoma. However, they are markedly different in terms of its physiologic and pathologic basis. CagA is 120-145-kDa protein of H. pylori and located one end of Cag PAI encoding components of type IV secretion system. H. pylori expressing CagA are associated with development of atrophic gastritis, peptic ulcer, and gastric carcinoma. This study was aimed to examine the differences of cagA mutations of H. pylori isolated from duodenal ulcer and gastric carcinoma. Methods: Isolated H. pylori from 29 patients with gastric carcinoma and 31 patients with duodenal ulcer were compared the frequency of mutations after cloning of cagA of H. pylori. Results: Even there were diverse mutations scattered on whole sequence of cagA, mutations were more frequent in amino acid sequence 200-400 and 850-1100. Amino acid loci G311, D371, M393, T899, and S1068 were mutated in more than half of patients regardless of diseases. The mutations of CagA in C-terminal area, especially Q889, T899, R952, A968, R997, K1034, Q1067, and S1068, were 20% or more frequent in H. pylorifrom duodenal ulcer than those from gastric carcinoma. EPIYA type was not different between the duodenal ulcer and gastric carcinoma. Conclusions: These results suggest that the mutations of cagA of H. pylori, especially in C-terminus are distinguishable between duodenal ulcer and gastric carcinoma.
Cardiovascular risk factor control among cancer survivors: A population-based survey
Authors: K. Enright, M. Krzyzanowska
Journal: Journal of Clinical Oncology (2009)

6535 Background: Cardiovascular disease is a major cause of morbidity and mortality in long-term survivors of cancer. Whereas the burden of cardiovascular disease has been described in cancer survivors, the control of modifiable cardiovascular risk factors in this population is unknown. Methods: We used the National Health and Nutrition Examination Survey (NHANES 1999–2006) data to examine the rate of control of modifiable cardiac risk factors amongst US cancer survivors compared with propensity matched adult controls with no history of cancer. The modifiable cardiac risk factors (blood pressure, cholesterol, BMI, exercise, smoking) were considered to be controlled if they met the AHA/ACC guideline recommendations. Results: A total of 1,227 cancer survivors and 3,672 age, sex, and comorbidity matched controls were identified, representing 11.9 million cancer survivors and 31.2 million controls. Compared to age, sex and comorbidity matched controls cancer survivors were more likely to be current smokers (34.5% vs. 28.8%, p = 0.021), and more likely to have their BMI at target (32.8% vs. 28.6%, p = 0.034). There was no significant difference in the rate of blood pressure control (69.4% vs. 69.2%, p = 0.88), cholesterol control (47.6% vs. 48.2%, p = 0.80) or adherence to exercise recommendations (24.4% vs. 24.6%, p = 0.89). Younger cancer survivors (age 20–40 y) were 2.8 times more likely to be smokers than controls, whereas older cancer survivors (age 60–80y) were 1.2 times more likely to be smokers than controls. Compared with recent cancer survivors (10 years from diagnosis) were more likely to have optimal blood pressure control (73.3% vs. 65.5%, p = 0.02), however there was no difference in smoking rates, cholesterol, exercise or weight control with duration of cancer survival. Conclusions: Overall the control of modifiable cardiac risk factors was similar between survivors and controls, but was suboptimal in both groups. This study identified smoking cessation, particularly amongst young cancers survivors, as an important area of focus for improvement in survivorship care. No significant financial relationships to disclose.