tbuckley/cabot-search huggingface dataset:
Iatrogenic immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide: A NABTT CNS Consortium study.
Authors: S. A. Grossman, X. Ye, G. J. Lesser, A. E. Sloan, C. Carson, S. Piantadosi
Journal: Journal of Clinical Oncology (2010)

2013 Background: Preliminary data suggest that the use of dexamethasone, radiation and temozolomide (TMZ) in high- grade gliomas (HGG) results in substantial immunosuppression. This prospective multicenter study serially followed CD4 counts and outcomes in this population. Methods: CD4 counts were obtained from patients with HGG before initiating standard radiation and TMZ and monthly thereafter for one year. Data on hospitalizations, infections, glucocorticoid doses, survival, and cause of death were recorded. Results: 96 patients with HGG were accrued and received TMZ: 84% had glioblastoma, 80% had debulking surgery, 50% were female, 97% were Caucasian, median age was 57, and median KPS was 90. The median CD4 count before starting radiation and TMZ was 664 which fell to 347, 255, and 288 at 1, 2, and 3 months. The CD4 count nadir occurred at 2 months when CD4 counts were < 300 in 73% of patients and < 200 in 40%. CD4 counts remained low during the year of follow-up with medians of 296, 311, and 310 at 4, 8, and 12 months. Reductions in CD4 counts were mirrored by total lymphocyte counts but independent of changes in WBC, RBC, or platelets. Patients with CD4 counts < 200 at 2 months had shorter survival than those with higher counts (median 13.1 versus 19.7 months, p = 0.002). The hazard ratio for death attributable to low CD4 count was 1.99 (p = 0.003) and after adjustment for relevant factors was 1.95 (p = 0.008). Median survival was related to the CTC toxicity grades for CD4 counts: grade 1 = 23.8 months, grade 2 = 19.7 months, grade 3-4 = 13.1 months (p = 0.009). Death occurred from disease progression in 88% of the patients and infection in only 2%. The only significant pretreatment predictor for low 2-month CD4 count was low baseline CD4 count (p = 0.025). Conclusions: Standard therapy of HGG results in severe CD4 count reductions that occur early, are long-lasting, and are prognostic for early death from tumor progression. These results support the routine monitoring of CD4 counts and have important implications for studies escalating TMZ doses or using vaccines. Future studies will determine the role of CD4 counts in modifying the duration of prophylactic antibiotics and the intensity and duration of TMZ. No significant financial relationships to disclose.
Multimodality Therapy of Localized Gastric Adenocarcinoma
Authors: Brian Badgwell
Journal: Journal of the National Comprehensive Cancer Network (2016)

Surgical resection is the primary method of obtaining a potential cure for patients with gastric adenocarcinoma. However, chemotherapy or chemoradiotherapy offer significant improvement in survival over surgery alone. Much of the difficulty in deciding the optimal treatment strategy is choosing between perioperative chemotherapy or adjuvant chemoradiotherapy. Adding to the complexity is the potential for incorporating treatment strategies based on clinical trials performed in Asia. There is likely a difference in tumor biology between Eastern and Western patients with gastric adenocarcinoma, in addition to the clear differences in screening, pathologic assessment, and surgical technique. Even among tumors in Western populations, heterogeneity of histology, anatomy, and staging among studies make cross-trial comparisons difficult. There is also active controversy surrounding the staging and management of gastroesophageal junction tumors. Lastly, the benefit of extended lymph node dissection is not clear based on the existing studies and has not been firmly established as a surgical standard of care for all patients. Future goals include better classification of gastric cancer, continued pursuit of randomized trials in Western populations, standardization of surgical technique, and incorporation of targeted therapies.
Improving the Physical Examination—Reply
Authors: William G. Nelson, Antony Rosen, Peter J. Pronovost
Journal: JAMA (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 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
Vitamin D over the first decade and susceptibility to childhood allergy and asthma
Authors: Elysia M. Hollams, Shu Mei Teo, Merci Kusel, Barbara J. Holt, Kathryn E. Holt, Michael Inouye, Nicholas H. De Klerk, Guicheng Zhang, Peter D. Sly, Prue H. Hart, Patrick G. Holt
Journal: Journal of Allergy and Clinical Immunology (2016)
Focal High Intensity Focused Ultrasound of Unilateral Localized Prostate Cancer: A Prospective Multicentric Hemiablation Study of 111 Patients
Authors: Pascal Rischmann, Albert Gelet, Benjamin Riche, Arnauld Villers, Gilles Pasticier, Pierre Bondil, Jean-Luc Jung, Hubert Bugel, Jacques Petit, Harry Toledano, Stéphane Mallick, Olivier Rouvière, Muriel Rabilloud, Hélène Tonoli-Catez, Sebastien Crouzet
Journal: European Urology (2016)
GRAFT FUNCTION FOLLOWING LIVER-TRANSPLANTATION IS DETERMINED BY THE DEGREE OF REPERFUSION INJURY AND IS PREDICTED EARLY BY INDOCYANINE GREEN CLEARANCE
Authors: Jn Plevris, K Bzeizi, R Jalan, M Dollinger, Alan Lee, Ndc Finlayson, Peter Hayes, John Plevris
Journal: Hepatology (1995)
Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic models
Authors: Marc Brisson, Élodie Bénard, Mélanie Drolet, Johannes A Bogaards, Iacopo Baussano, Simopekka Vänskä, Mark Jit, Marie-Claude Boily, Megan A Smith, Johannes Berkhof, Karen Canfell, Harrell W Chesson, Emily A Burger, Yoon H Choi, Birgitte Freiesleben De Blasio, Sake J De Vlas, Giorgio Guzzetta, Jan A C Hontelez, Johannes Horn, Martin R Jepsen, Jane J Kim, Fulvio Lazzarato, Suzette M Matthijsse, Rafael Mikolajczyk, Andrew Pavelyev, Matthew Pillsbury, Leigh Anne Shafer, Stephen P Tully, Hugo C Turner, Cara Usher, Cathal Walsh
Journal: The Lancet Public Health (2016)

Modelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination.
Enterococcus hirae and Barnesiella intestinihominis Facilitate Cyclophosphamide-Induced Therapeutic Immunomodulatory Effects
Authors: Romain Daillère, Marie Vétizou, Nadine Waldschmitt, Takahiro Yamazaki, Christophe Isnard, Vichnou Poirier-Colame, Connie P.M. Duong, Caroline Flament, Patricia Lepage, Maria Paula Roberti, Bertrand Routy, Nicolas Jacquelot, Lionel Apetoh, Sonia Becharef, Sylvie Rusakiewicz, Philippe Langella, Harry Sokol, Guido Kroemer, David Enot, Antoine Roux, Alexander Eggermont, Eric Tartour, Ludger Johannes, Paul-Louis Woerther, Elisabeth Chachaty, Jean-Charles Soria, Encouse Golden, Silvia Formenti, Magdalena Plebanski, Mutsa Madondo, Philip Rosenstiel, Didier Raoult, Vincent Cattoir, Ivo Gomperts Boneca, Mathias Chamaillard, Laurence Zitvogel
Journal: Immunity (2016)
Oncogenic Functions of Gli1 in Pancreatic Adenocarcinoma Are Supported by Its PRMT1-Mediated Methylation
Authors: Yan Wang, Jung-Mao Hsu, Ya'an Kang, Yongkun Wei, Pei-Chih Lee, Shing-Jyh Chang, Yi-Hsin Hsu, Jennifer L. Hsu, Hung-Ling Wang, Wei-Chao Chang, Chia-Wei Li, Hsin-Wei Liao, Shih-Shin Chang, Weiya Xia, How-Wen Ko, Chao-Kai Chou, Jason B. Fleming, Huamin Wang, Rosa F. Hwang, Yue Chen, Jun Qin, Mien-Chie Hung
Journal: Cancer Research (2016)

The oncogenic transcription factor Gli1 is a critical effector in the Hedgehog (Hh) pathway, which is necessary for the development and progression of pancreatic ductal adenocarcinoma (PDAC). Although TGFβ and K-Ras are known regulators of Gli1 gene transcription in this setting, it is not understood how Gli1 functional activity is regulated. Here, we report the identification of Gli1 as a substrate for the protein arginine N-methyltransferase PRMT1 in PDAC. We found that PRMT1 methylates Gli1 at R597, promoting its transcriptional activity by enhancing the binding of Gli1 to its target gene promoters. Interruption of Gli1 methylation attenuates oncogenic functions of Gli1 and sensitizes PDAC cells to gemcitabine treatment. In human PDAC specimens, the levels of both total Gli1 and methylated Gli1 were correlated positively with PRMT1 protein levels. Notably, PRMT1 regulated Gli1 independently of the canonical Hh pathway as well as the TGFβ/Kras-mediated noncanonical Hh pathway, thereby signifying a novel regulatory mechanism for Gli1 transcriptional activity. Taken together, our results identified a new posttranslational modification of Gli1 that underlies its pivotal oncogenic functions in PDAC. Cancer Res; 76(23); 7049-58. ©2016 AACR.
A randomized phase II study of irinotecan, 5-fluorouracil, and folinic acid (FOLFIRI) with or without the addition of an endothelin receptor antagonist in patients with metastatic colorectal cancer after failure of oxaliplatin-containing chemotherapy.
Authors: A. L. Thomas, R. H. Wilson, W. P. Steward, R. A. Adams, S. E. Bridges, A. C. Casbard, T. Maughan, G. Griffiths
Journal: Journal of Clinical Oncology (2011)

TPS161 Background: Plasma endothelin-1 levels are elevated in CRC patients and are prognostic for worse outcome. Endothelin-A receptor (ETAR) expression is increased in CRC samples compared with normal tissue. Antagonism of ETAR enhances cytotoxicity when combined pre-clinically with chemotherapeutics (Growcott JW, 2009. Anticancer Drugs 20: 83-88). We hypothesize that the anti-tumour activity of irinotecan and 5-FU (FOLFIRI regimen) can be increased by simultaneously blocking cell survival signalling through ETAR. Methods: This trial is exploring the specific ETAR antagonist zibotentan or placebo combined with FOLFIRI administered for 24 weeks in second-line treatment of metastatic CRC. Patients are >18 years with RECIST measurable disease, ECOG PS0-1, good end-organ function, and no previous Irinotecan use. After chemotherapy, patients may continue zibotentan or placebo monotherapy. This is a double blind (1:1) randomised phase II trial. The dose of zibotentan is 10mg orally once daily. 56 of 122 planned patients have been enrolled to date. The control arm will enable direct comparison of toxicity and will provide an estimate of PFS to support the design of a future phase III trial. The primary objective is to establish the anti-tumour activity of zibotentan with FOLFIRI as measured by PFS (time-to-event). Secondary objectives are to determine the toxicity and feasibility of the combination, and to collect tumour and blood samples for future translational work. The predicted median PFS for patients on FOLFIRI chemotherapy is 16 weeks. 122 participants are required to demonstrate a statistically significant difference between arms. This is an academically led collaborative trial between the UK National Cancer Research Network and AstraZeneca, which is endorsed by Cancer Research UK (CRUKE/09/023) and coordinated by the CR UK Wales Cancer Trials Unit in Cardiff University, UK. The ISRCTN number is 73199181.
A novel rapid genetic diagnosis for peritoneal recurrence in gastrointestinal cancer patients
Authors: H. Iinuma, K. Okinaga, T. Watanabe, R. Fukushima, T. Inaba, T. Mimura, K. Matsuda, S. Ohnaka, T. Hayashi
Journal: Journal of Clinical Oncology (2007)

21052 Background: The prediction of peritoneal recurrence in gastrointestinal cancer patients is extremely important in order to prevent an unfavorable prognosis. The aim of our study was to evaluate the usefulness of a novel rapid RNA amplification system with transcription-reverse transcription concerted reaction (TRC) to detect isolated tumor cells in peritoneal washes of gastrointestinal cancer patients as an intra-operative genetic predictor of peritoneal recurrence. To clarify the characteristic qualities of TRC, we compared the results with those of one-step real-time RT-PCR. Methods: A total of 325 cytology-negative gastrointestinal cancer patients (164 gastric cancer, 161 colorectal cancer) were included. This study was approved by the institutional review board of our hospital and all patients provided written informed consent. Peritoneal washes of Douglas cavity were collected from patients. One-half of each wash was used for cytopathology and the other half was used for molecular diagnosis. Total RNA was extracted from cells which were separated from washes, and TRC and one-step real-time RT-PCR of multiple marker genes (CEA, CK20 mRNA) were performed using a TRCRapid-160 and LightCycler, respectively. Results: The rapidity and simplicity of the TRC is superior to that of one-step real-time RT-PCR. The detection time of marker genes by TRC was only 20 minutes as compared to 70 minutes of real-time RT-PCR. The sensitivity and reproducibility of the TRC were equal to those of real-time RT-PCR. Molecular detection of CEA and/or CK20 transcripts of the peritoneal washes by TRC showed a significant correlation to the depth of invasion, venous invasion, lymph node invasion, lymph node metastasis, peritoneal metastasis and stage. The peritoneal recurrence- free and overall survival rates of CEA and/or CK20 transcript-positive patients were significantly shorter than those of marker gene-negative patients. CEA and/or CK20 transcripts in peritoneal washes were independent prognostic factors of peritoneal recurrence-free survival and overall survival. Conclusion: TRC may be more useful than real-time RT-PCR due to its rapidity and simplicity for the intra-operative genetic diagnosis of peritoneal recurrence in patients with gastric and colorectal cancer. No significant financial relationships to disclose.
Using standardized patients to improve delivery of bad news by pediatric hematology-oncology fellows.
Authors: Julienne Brackett, Ernest Frugé, Martin Lorin
Journal: Journal of Clinical Oncology (2015)

29 Background: First-year pediatric hematology-oncology fellows frequently must deliver difficult news to patients and families, possibly with little prior experience. Training in this area is often via didactic lectures and by “trial and error”. This can lead to significant discomfort on the part of fellows and potentially increased distress on the part of families if information is poorly communicated. Standardized patient (SP) encounters provide a safe environment for fellows to practice effective and compassionate communication skills. SPs can provide feedback to the fellows that may not otherwise be available from patients, families or peers. Methods: During the 4 hour course, fellows receive didactic sessions on delivery of bad news, disclosure of medical errors, and discussion of prognosis and goals of care. Half of the fellows receive the didactic sessions, while the other half participate in the SP cases involving 7-10 minute encounters followed by 10-15 minute confidential debriefings including the fellow, SP and a faculty member. Three cases are completed by each fellow: new diagnosis of an incurable brain tumor, tumor progression and goals of care discussion regarding the same patient 6 months later, and disclosure of a chemotherapy error. At the end, fellows complete an evaluation of the course and their perceived post-course skills. Results: Fellows in the first course (n = 8) strongly agreed that the course improved their ability to deliver bad news (mean = 5 on 5 point scale), was an appropriate method for this material (mean = 4.6) and that the confidential debriefing was useful without being stressful (mean = 4.7). Most comments supported the utility of receiving immediate feedback from the SPs and faculty. The didactic sessions were listed as the least helpful part of the course. Conclusions: Simulated encounters with immediate feedback from SPs and faculty can improve perceived competence in the delivery of bad news. Like many adult learners, course participants did not find the didactic sessions to be as helpful as interactive experiences. Follow-up surveys after the fellows complete the first year of training will further assess the utility of this instructional method.
In Vitro Topographical Model of Fuchs Dystrophy for Evaluation of Corneal Endothelial Cell Monolayer Formation
Authors: Muhammad Rizwan, Gary S. Peh, Khadijah Adnan, Sacha L. Naso, Alon R. Mendez, Jodhbir S. Mehta, Evelyn K. F. Yim
Journal: Advanced Healthcare Materials (2016)

A common indication for corneal transplantation, which is the most transplanted tissue, is a dysfunctional corneal endothelium due to Fuchs' endothelial dystrophy (FED). FED is diagnosed by the presence of in vivo pathological microtopography on the Descemet membrane, which is called corneal guttata. Minimally invasive corneal endothelial cell regenerative procedures such as endothelial cell injection therapy and Rho kinase inhibitor pharmacotherapy have been proposed as alternatives to conventional corneal transplantation for FED patients. However, the effect of guttata on monolayer reformation following such therapies is unknown and there is no equivalent in vitro or animal model to study monolayer reformation. Using a synthetic guttata FED disease model, the formation of the monolayer is investigated to evaluate the efficacy of both therapies. Results obtained suggest that guttata dimensions, density, and spacing greatly affect the fate of corneal endothelial cells in terms of migratory behavior and monolayer reformation. Densely packed synthetic guttata mimicking late‐stage FED hinders monolayer reformation, while synthetic guttata of lower height and density show improved monolayer formation. These results suggest that severity of the FED, as determined by height and density of existing guttata, can potentially attenuate corneal endothelial monolayer formation of corneal cell injection therapy and pharmacotherapy.
Staphylococcus aureus enterotoxin B activates airway epithilial cells for chemokine and growth factor release, with prolonged survival and migration of granulocytes in vitro
Authors: Kristien Reekmans, Greet Hens, Dominique Bullens, Sonja Bobic, C Bachert, Jan Ceuppens, Peter Hellings
Journal: Allergy (2007)
A randomized phase II study of paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus and ixabepilone/carboplatin/bevacizumab as initial therapy for measurable stage III or IVA, stage IVB or recurrent endometrial cancer, GOG-86P.
Authors: Carol Aghajanian, Virginia L. Filiaci, Don S. Dizon, Jay Carlson, Matthew A. Powell, Angeles Alvarez Secord, Krishnansu Sujata Tewari, David Bender, David M. O'Malley, Ashley Stuckey, Jacob Rotmensch, Douglas A. Levine, Heather A. Lankes, Kathleen N. Moore
Journal: Journal of Clinical Oncology (2015)

5500 Background: Paclitaxel (PC) is a standard initial therapy for advanced endometrial cancer (EC). We evaluated efficacy and tolerability of incorporating three novel agents into initial therapy. Methods: Patients (pts) had received no prior chemotherapy. Randomization (1:1:1) was stratified by measurable disease, recurrent disease, prior pelvic RT. Primary endpoint was progression-free survival (PFS). GOG 209 was used as historical control. Results: At least 70% received 6 cycles of C (70-83%) or P (74-82%); 68% received 6 cycles of I. Pts on arm 1 received a median of 12 cycles (0 - 78) of Bev compared with 9 cycles (0-53) on arm 3. A median of 8 cycles (0-62) of Tem was given on arm 2. Hypertension (G 3/4) was more common in the Bev arms (16%) than in the Tem arm (3%), p = 0.001. Pneumonitis (p = 0.004) and oral mucositis (p < 0.001), were more common in the Tem arm. PFS, compared using a log-rank test on data grouped by time intervals, was not significantly increased in any experimental arm (p > 0.039) when each arm was compared to historical control. HR (92% CI) for arms 1, 2 and 3 was 0.81 (0.63-1.02), 1.22 (0.96-1.55) and 0.87 (0.68-1.11), respectively. Overall survival (OS) censoring at 36 months, a secondary endpoint, was statistically significantly (p < 0.039) increased in arm 1 relative to control but was not significantly increased in arms 2 or 3 (HR (92% CI) arms 1, 2 and 3 was 0.71 (0.55-0.91), 0.99 (0.78-1.26) and 0.97 (0.77-1.23)). Conclusions: PFS is not significantly increased in any Arm. OS is significantly increased in the PC + Bev arm. Clinical trial information: NCT00977574. Arm 1 PC + Bev Arm 2 PC + Tem Arm 3 IC + Bev Enrolled (N = 349) 116 115 118 Eligible and Treated (N = 329) 108 111 110 Median Age 62 63 65 PS 0-1 106 (91%) 109 (95%) 113 (96%) Stage III 12 (10%) 13 (11%) 10 (9%) IV 58 (50%) 58 (51%) 62 (52%) Recurrent 46 (40%) 44 (38%) 46 (39%) Prior Pelvic RT No 99 (85%) 95 (83%) 98 (83%) Yes 17 (15%) 20 (17%) 20 (17%) Measurable Disease No 27 (23%) 30 (26%) 33 (28%) Yes 89 (77%) 85 (74%) 85 (72%) Histology Endometrioid G 1 17 (15%) 13 (11%) 15 (13%) Endometrioid G 2 36 (31%) 24 (21%) 27 (23%) Endometrioid G 3 30 (26%) 30 (26%) 22 (19%) Serous 16 (14%) 26 (23%) 31 (26%) Clear Cell 6 (5%) 4 (3%) 6 (5%) Other 11 (9%) 18 (16%) 17 (14%) RR (GOG209 51%) 60% 55% 53%