tbuckley/cabot-search huggingface dataset:
Tumor necrosis factor alpha (TNFα) induces proliferation of breast cancer cells by a mechanism that requires TNF receptor type 1 (TNFR1) and type 2 (TNFR2)
Authors: Martin A. Rivas, Romina P. Carnevale, Cinthia Rosemblit, Mariana Salatino, Cecilia J. Proietti, Wendy Béguelin, Eduardo H. Charreau, Wim A. Buurman, Patricia V. Elizalde, Roxana Schillaci
Journal: Cancer Research (2006)

1648  IGF-1 is a potent growth factor for small cell lung cancer (SCLC) in the autocrine and endocrine context. Inhibition of IGF-1R kinase activity with a small molecule inhibitor, NVP-ADW-742, resulted in growth inhibition and induction of apoptosis of sensitive cell lines (H146, H526) and in synergistic growth inhibition with a c-Kit inhibitor (imatinib) in more resistant cell lines (H209, WBA, H69). A similar pattern of response is seen when H146 or H526 cells were treated with a blocking IGF-1R monoclonal antibody (IMC-A12). To determine why SCLC cells are so responsive to IGF-1, IGF-1 signaling in SCLC cells was compared to that in the immortalized non-tumorigenic bronchial epithelial cell line BEAS-2B. Following IGF-1 stimulation, Akt activation in BEAS-2B was noted to decay within 30 min and return to baseline by 6 hrs, whereas Akt activation in the H526 cell line did not decay for at least 6 hrs. Since c-Kit-mediated Akt activation in H526 returned to baseline within 1 hr of SCF treatment the defect in IGF-1 signaling does not appear to be within the PI3K-Akt pathway. Studies of IGF-1R phosphorylation demonstrated that while IGF-1-stimulated phosphorylation decayed by 70-80% within 30 min and returned to baseline within 2 hrs in BEAS-2B cells, IGF-1R phosphorylation remained elevated without decay for at least 24 hrs in H526 cells. No mutations were found in the IGF-1R kinase domain to account for aberrant inactivation. PTP1B is thought to be the major phosphatase involved in IGF-1R dephosphorylation. Since PTP1B is localized in endosomes, receptor internalization is thought to be required for IGF-1R inactivation. Caveolin-1 (Cav-1) has been implicated in IGF-1R internalization and SCLC has been shown to express little if any Cav-1 whereas BEAS-2B expresses high levels of Cav-1. Re-expression of Cav-1 in H526 cells using a constitutive or regulated promoter modestly enhanced decay of IGF-1 signaling but still did not approximate the rapid decay kinetics seen in BEAS-2B. This suggests that in addition to loss of Cav-1 expression, additional defects in IGF-1R inactivation are present. Study of the predominant IGF-1R phosphatases PTP1B and SHP-2 in a panel of SCLC cell lines demonstrated similar expression levels and activity to that in BEAS-2B. Other potential mechanisms for deregulated IGF-1R inactivation are currently being explored.
Incidence of second primary malignancies in veterans after prostate cancer diagnosis.
Authors: Narjust Perez-Florez, Larysa Jessica Gromko, Melanie L. Gonzalez, Shanti Srinivas, Victor Tsu-Shih Chang, Fengming Zhong, Jan Einhorn, Barbara Crump, Emma R Paz-Querubin, Basil Kasimis
Journal: Journal of Clinical Oncology (2014)

5093 Background: With the advancement of diagnostic and treatment modalities in prostate cancer (PC) over the past 20 years, PC specific survival rates have improved. The aim of this study was to evaluate the incidence of second primary malignancies in our veteran population after diagnosis of PC. Methods: We reviewed the records of 548 patients (pts) diagnosed with PC between 1999 and 2011. Data including demographics, veteran status (Vietnam vs. non-Vietnam), Gleason score, PSA, PC stage, treatment, incidence of second primary malignancy and survival were studied. Cox regression analysis was performed using SAS v 9.2. Results: There were 548 pts with a median (M) age of 71 years (45-98). 265 pts (48%) were Caucasian, 256 pts (47%) African American and 28 pts (5%) of other races; 158 pts (31%) were Vietnam veterans. The M Gleason score was 7 (4-10) and PSA 9.3 (0.7-7870). 153 pts (28%) had one or more second primary malignancies after PC diagnosis. The incidence of second malignancy was significantly higher among Vietnam veterans (OR: 2.08, p<0.0003) and pts with localized PC (OR: 5.53, p<0.0001) in univariate analysis. Sites for second malignancy were lung 42 (28%), hematologic 21 (14%), bladder 19 (12%), colorectal 11 (7%) and liver 10 (6.5%). Of the 95 pts who received radiotherapy for PC and later developed a second malignancy, 28 (29%) developed the second malignancy in the radiotherapy field (bladder, colon and rectal cancer) and 12 (11%) developed a hematologic malignancy. In 72 (47%) pts the second malignancy was diagnosed ≥4 years after the diagnosis of PC, 62 (41%) between 1-3 years and 18 (12%) within 12 months of the diagnosis of PC. Age (OR: 0.95, 95% CI: 0.93-0.97, p<0.0001), PC stage (OR: 0.18, 95% CI: 0.08-0.38, p<0.0001) and veteran status (Vietnam vs. non-Vietnam; OR: 1.65, 95% CI: 1.07-2.55, p<0.02) were independent and significant predictors of a second primary malignancy by multivariate analysis. Conclusions: In this cohort, 28% of veterans with prior PC developed a second primary malignancy. Vietnam veterans had 1.7 times greater risk to develop a second primary malignancy and patients with localized PC had 18% higher risk of developing a second primary malignancy compared to patients with metastatic PC.
Direct-to-Consumer Atrial Fibrillation Screening
Authors: Erik A. Wallace
Journal: JAMA Internal Medicine (2019)

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 Internal Medicine 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 Internal Medicine journal
Treatment Choices and Outcomes for Patients with Multiple Myeloma after Relapse on Lenalidomide Maintenance Therapy: Results from the Connect® MM Registry
Authors: Sundar Jagannath, Mohit Narang, Sikander Ailawadhi, Robert M Rifkin, Howard R Terebelo, Kathleen Toomey, Brian GM Durie, James W Hardin, Cristina J Gasparetto, Lynne Wagner, James Omel, Shankar Srinivasan, Amani Kitali, Amit Agarwal, Rafat Abonour
Journal: Blood (2018)
Contemporary Use and Trends in Unprotected Left Main Coronary Artery Percutaneous Coronary Intervention in the United States
Authors: Javier A. Valle, Hector Tamez, J. Dawn Abbott, Issam D. Moussa, John C. Messenger, Stephen W. Waldo, Kevin F. Kennedy, Frederick A. Masoudi, Robert W. Yeh
Journal: JAMA Cardiology (2019)

<h3>Importance</h3> Recent data support percutaneous revascularization as an alternative to coronary artery bypass grafting in unprotected left main (ULM) coronary lesions. However, the relevance of these trials to current practice is unclear, as patterns and outcomes of ULM percutaneous coronary intervention (PCI) in contemporary US clinical practice are not well studied. <h3>Objective</h3> To define the current practice of ULM PCI and its outcomes and compare these with findings reported in clinical trials. <h3>Design, Setting, and Participants</h3> This cross-sectional multicenter analysis included data collected from 1662 institutions participating in the National Cardiovascular Data Registry (NCDR) CathPCI Registry between April 2009 and July 2016. Data were collected from 33 128 patients undergoing ULM PCI and 3 309 034 patients undergoing all other PCI. Data were analyzed from June 2017 to May 2018. <h3>Main Outcomes and Measures</h3> Patient and procedural characteristics and their temporal trends were compared between ULM PCI and all other PCI. In-hospital major adverse clinical events (ie, death, myocardial infarction, stroke, and emergent coronary artery bypass grafting) were compared using hierarchical logistic regression. Characteristics and outcomes were also compared against clinical trial cohorts. <h3>Results</h3> Of the 3 342 162 included patients, 2 223 570 (66.5%) were male, and the mean (SD) age was 64.2 (12.1) years. Unprotected left main PCI represented 1.0% (33 128 of 3 342 162) of all procedures, modestly increasing from 0.7% to 1.3% over time. The mean (SD) annualized ULM PCI volume was 0.5 (1.5) procedures for operators and 3.2 (6.1) procedures for facilities, with only 1808 of 10 971 operators (16.5%) and 892 of 1662 facilities (53.7%) performing an average of 1 or more ULM PCI annually. After adjustment, major adverse clinical events occurred more frequently with ULM PCI compared with all other PCI (odds ratio, 1.46; 95% CI, 1.39-1.53). Compared with clinical trial populations, patients in the CathPCI Registry were older with more comorbid conditions, and adverse events were more frequent. <h3>Conclusions and Relevance</h3> Use of ULM PCI has increased over time, but overall use remains low. These findings suggest that ULM PCI occurs infrequently in the United States and in an older and more comorbid population than that seen in clinical trials.
Abstract 15595: Improved Clinical Performance and Teamwork of Pediatric Interprofessional Resuscitation Teams With a Simulation-Based Educational Intervention
Authors: Elaine Gilfoyle, Deanna Koot, John Annear, Farhan Bhanji, Adam Cheng, Jonathan Duff, Vincent Grant, Cecilia St George-Hyslop, Nicole Delaloye, Afrothite Kotsakis, Carolyn McCoy, Christa Ramsay, Matthew Weiss, Ronald Gottesman
Journal: Circulation (2015)

Introduction: Human errors occur during resuscitation despite individual knowledge of resuscitation guidelines. Poor teamwork has been implicated as a major source of such error; therefore interprofessional resuscitation teamwork training is essential. Hypothesis: A one-day team training course for pediatric interprofessional resuscitation team members improves adherence to PALS guidelines, team efficiency and teamwork in a simulated clinical environment. Methods: A prospective interventional study was conducted at 4 children’s hospitals in Canada with pediatric resuscitation team members (n=300, 51 teams). Educational intervention was a one-day simulation-based team training course involving interactive lecture, group discussions and 4 simulated resuscitation scenarios followed by debriefing. First scenario of the day was conducted prior to any training. Final scenario of the day was the same scenario, with modified patient history. Scenarios included standardized distractors designed to elicit and challenge specific teamwork behaviors. Primary outcome measure was change (before and after training) in adherence to PALS guidelines, as measured by the Clinical Performance Tool (CPT). Secondary outcome measures: change in times to initiation of chest compressions and defibrillation; and teamwork performance, as measured by the Clinical Teamwork Scale (CTS). Correlation between CPT and CTS scores was analyzed. Results: Teams significantly improved CPT scores (67.3% to 79.6%, P&lt; 0.0001), time to initiation of chest compressions (60.8 sec to 27.1 sec, P&lt;0.0001), time to defibrillation (164.8 sec to 122.0 sec, P&lt;0.0001) and CTS scores (56.0% to 71.8%, P&lt;0.0001). Significantly more teams defibrillated under AHA target of 2 minutes (10 vs. 27, P&lt;0.01). A strong correlation was found between CPT and CTS (r=0.530, P&lt;0.0001). Conclusions: Participation in a simulation-based team training educational intervention significantly improved surrogate measures of clinical performance, time to initiation of key clinical tasks, and teamwork during simulated pediatric resuscitation. A strong correlation between clinical and teamwork performance suggests that effective teamwork optimizes clinical performance of resuscitation teams.
Enamel biomimetics—fiction or future of dentistry
Authors: Mirali Pandya, Thomas G. H. Diekwisch
Journal: International Journal of Oral Science (2019)

Tooth enamel is a complex mineralized tissue consisting of long and parallel apatite crystals configured into decussating enamel rods. In recent years, multiple approaches have been introduced to generate or regenerate this highly attractive biomaterial characterized by great mechanical strength paired with relative resilience and tissue compatibility. In the present review, we discuss five pathways toward enamel tissue engineering, (i) enamel synthesis using physico-chemical means, (ii) protein matrix-guided enamel crystal growth, (iii) enamel surface remineralization, (iv) cell-based enamel engineering, and (v) biological enamel regeneration based on de novo induction of tooth morphogenesis. So far, physical synthesis approaches using extreme environmental conditions such as pH, heat and pressure have resulted in the formation of enamel-like crystal assemblies. Biochemical methods relying on enamel proteins as templating matrices have aided the growth of elongated calcium phosphate crystals. To illustrate the validity of this biochemical approach we have successfully grown enamel-like apatite crystals organized into decussating enamel rods using an organic enamel protein matrix. Other studies reviewed here have employed amelogenin-derived peptides or self-assembling dendrimers to re-mineralize mineral-depleted white lesions on tooth surfaces. So far, cell-based enamel tissue engineering has been hampered by the limitations of presently existing ameloblast cell lines. Going forward, these limitations may be overcome by new cell culture technologies. Finally, whole-tooth regeneration through reactivation of the signaling pathways triggered during natural enamel development represents a biological avenue toward faithful enamel regeneration. In the present review we have summarized the state of the art in enamel tissue engineering and provided novel insights into future opportunities to regenerate this arguably most fascinating of all dental tissues.
Incorporating PARP inhibitors in translational studies for Ewing’s sarcoma.
Authors: David Ross Goshorn, Elizabeth Stewart, Anang Shelat, Michael A. Dyer, Cori Bradley, Alberto S. Pappo
Journal: Journal of Clinical Oncology (2014)

e21025 Background: Ewing’s Sarcoma (EWS) is an aggressive solid tumor of the bone and soft tissue affecting nearly 250 adolescents and young adults each year. Prior research has demonstrated sensitivity of cell lines bearing the pathognomonic EWS-FLI1 translocation to poly ADP ribose polymerase inhibitors (PARPi). Single agent PARPi is unlikely to provide clinical response without the addition of DNA damaging agents. We therefore examined the single agent cytotoxicity of olaparib, veliparib, and BMN 673 as well as the cytotoxicity obtained with the combination with either irinotecan (SN-38) or temozolomide (TMZ). Additionally we have created a unique, clinically relevant EWS orthotopic xenograft mouse model for in vivo evaluation. Methods: EWS cell lines were optimized for 7 day in vitrohigh throughput analysis. Individual cell lines were exposed to each PARPi in dose response and also in combination with SN-38 or temozolomide in dose response. Cell viability was measured after 7 days via CellTiter-Glo. A murine orthotopic xenograft was created by injecting tumor cells suspended in matrigel into the femur marrow cavity of CD-1 nude mice. Results: Single agent cytotoxicity was achieved with all agents, however dramatic variability was noted in drug concentrations required to attain cytotoxicity. The greatest cytotoxic effect was obtained with BMN 673 followed by olaparib and veliparib. When combined with SN-38 there was a dramatic decrease in EC50 in all lines tested with all PARPi tested. When combined with TMZ the effect was less dramatic and seen only in combination with BMN 673. Conclusions: The combination of irinotecan to BMN 673, olaparib and veliparib provides superior in vitro cytotoxicity when compared to PARPi alone. We now have a clinically relevant orthotopic murine xenograft to test the in vitro results. The full understanding of pharmacokinetics will be critical to help identify the best pairing of cytotoxic agents to move forward in our orthotopic xenograft model.
A phase II study of medroxyprogesterone acetate plus metformin as fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer.
Authors: Akira Mitsuhashi, Hirokazu Usui, Yasunori Satoh, Takako Kiyokawa, Makio Shozu
Journal: Journal of Clinical Oncology (2014)

5592 Background: Metformin, a drug widely used in the treatment of type 2 diabetes mellitus, has been shown to reduce the risk of cancer and relapse after treatment. To determine whether the concomitant use of metformin prevents recurrence after progestin therapy, we conducted a phase II study of medroxyprogesterone acetate (MPA) plus metformin as fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer. Methods: Patients with endometrial cancer or atypical endometrial hyperplasia were treated with MPA (400 mg/day) and metformin (750 mg up to 2250 mg/day) for 24 weeks. In cases of partial histological regression but remarkable hormonal effects (partial response, PR), treatment was continued for another 12 weeks. Metformin was administered until conception, even after MPA was discontinued. The primary endpoint was the relapse rate after remission, and the secondary endpoints were the overall response rate and safety profile. An independent data and safety monitoring committee performed an interim analysis of efficacy and safety at 12 months after the completion of enrollment. Results: From July 2009 to December 2012, 36 patients (17 with endometrial cancer and 19 with atypical endometrial hyperplasia) were enrolled. Most patients were obese and had insulin resistance; the mean body mass index was ≥25 in 28 patients (mean, 31 kg/m2; range, 19–51 kg/m2) and the homeostasis model assessment for insulin resistance index was ≥2.5 in 25 patients (mean, 4.8; range, 0.7–21). One patient showed progression at 12 weeks (2.8%). At 36 weeks, 31 patients (86.1%) had achieved complete response (CR) and the remaining 4 (11.1%) had achieved PR. During a median follow-up period of 34 months (range, 12–54 months), relapse was confirmed in 2 of the 31 patients who had achieved CR, resulting in a relapse rate of 6.4% compared to a previously reported rate of 30-50% without metformin. The 3-year estimated relapse-free survival rate was 93%. None of the patients experienced severe toxicity. Conclusions: The use of metformin inhibited disease relapse after progestin therapy. Clinical trial information: UMIN 000002210.
A saliva-based rapid test to quantify the infectious subclinical malaria parasite reservoir
Authors: Dingyin Tao, Brent McGill, Timothy Hamerly, Tamaki Kobayashi, Prachi Khare, Amanda Dziedzic, Tomasz Leski, Andrew Holtz, Bruce Shull, Anne E. Jedlicka, Andrew Walzer, Paul D. Slowey, Christopher C. Slowey, Sandrine E. Nsango, David A. Stenger, Mike Chaponda, Modest Mulenga, Kathryn H. Jacobsen, David J. Sullivan, Sadie J. Ryan, Rashid Ansumana, William J. Moss, Isabelle Morlais, Rhoel R. Dinglasan
Journal: Science Translational Medicine (2019)

A noninvasive malaria rapid test assesses subclinical carriage of Plasmodium falciparum (human malaria) parasites at the point of need.
Non-sugar sweeteners and health
Authors: Vasanti S Malik
Journal: BMJ (2019)

The weight of evidence hints at benefits, but the full picture has yet to emerge

There is much public and scientific interest in whether foods and beverages containing non-sugar sweeteners (NSS)—which contain few or no calories—should be recommended as a strategy to reduce consumption of free sugars, particularly sugar sweetened beverages. However, inconsistent research findings and potential safety concerns have hampered official guidance.1

To clarify the benefits and harms of NSS consumption and to inform WHO guidance, Toews and colleagues conducted a systematic review and meta-analysis evaluating the effect of NSS intake on a broad range of health outcomes in adults and children (doi:10.1136/bmj.k4718).2 They included 56 interventional and observational studies, making this review the most comprehensive on this topic so far.

Among adults, findings from the few trials comparing NSS intake with sugar intake suggested small improvements in body mass index and fasting concentrations of blood glucose favouring NSS. Among children, NSS intake led to a smaller increase in body mass index z score than sugar intake, but NSS made no difference to body weight. For most other outcomes, no statistically …
No Utility of Routine Laboratory Testing during Surveillance in Detecting Relapse in Patients with Classic Hodgkin Lymphoma in First Remission
Authors: Ryan C. Lynch, Vandana Sundaram, Manisha Desai, Solomon Henry, Douglas Wood, Sarah Daadi, Karen S. Corbelli, Saul Rosenberg, Richard T Hoppe, Ranjana Advani
Journal: Blood (2018)
Comprehensive analysis of demographics and survival of pediatric medulloblastoma.
Authors: Therese A. Dolecek, Jigisha P. Thakkar, Katie E Long, John L. Villano
Journal: Journal of Clinical Oncology (2014)

2100 Background: We evaluated the American College of Surgeon’s National Cancer Data Base (NCDB) to describe current hospital-based epidemiologic frequency and survival patterns of pediatric medulloblastoma. Methods: We analyzed NCDB 1998-2010 data on medulloblastoma defined as ICD-0-3 histology codes 9470, 9471, 9474 diagnosed in primary site brain codes C71.0-C71.9 for children ages 0-19 years. Demographic variables analyzed were age, gender, race and Hispanic origin. Comparisons were also made among histologic subtypes and primary site. Frequencies and Kaplan-Meier relative survival estimates were generated using SEER*Stat software version 8.1.2. Results: A total of 3,067 cases of medulloblastoma were identified. Among pediatric age groups, frequency was highest for 5-9 years and lowest in infants. Males were observed to have higher incidence than females. Whites had highest counts among race groups and non-Hispanics were observed to have more frequent diagnoses than Hispanics. The most common histologic subtype was classic medulloblastoma (9470), accounting for 88.2% cases. More than 75% of cases occurred in infratentorial sites C71.6 (cerebellum) or C71.7 (brain stem). Better relative survival was observed as age at diagnosis increased. Females were observed to have better survival than males. No significant differences in survival were observed among race or origin groups. Statistically significantly better 5-year relative survival was observed for cases diagnosed with histologic subtypes 9470 (75.5%) and 9471 (desmoplastic, 79.6%) than 9474 (anaplastic/large cell, 50.6%). Site at diagnosis did not appear to influence survival time for medulloblastoma. Conclusions: We report an extensive demographic and survival analysis of pediatric medulloblastoma. Observed differences likely reflect biology across age, gender, race and origin groups.