tbuckley/cabot-search huggingface dataset:
Assessment of wheezing frequency and viral etiology on childhood and adolescent asthma risk
Authors: Halie M. Anderson, Robert F. Lemanske, Michael D. Evans, Ronald E. Gangnon, Tressa Pappas, Kris Grindle, Yury A. Bochkov, James E. Gern, Daniel J. Jackson
Journal: Journal of Allergy and Clinical Immunology (2016)
A phase I study of S-1 administration and a 24-h infusion of cisplatin plus paclitaxel in patients with advanced gastric cancer
Authors: H. Iwase, M. Shimada, T. Tsuzuki, M. Okeya, K. Kobayashi, Y. Hibino, H. Watanabe, Y. Horiuchi, H. Goto
Journal: Journal of Clinical Oncology (2006)

4074 Background: S-1 may have a major role in the treatment of gastric cancer as single agent or as a component of combination chemotherapy in Japan. We previously reported a multicentric phase II study of S-1 combined with a 24-h infusion of cisplatin in patients with advanced gastric cancer. This combination was active, safe and had the possibility of being combined with other anticancer drug. Combination chemotherapy with S-1 and cisplatin plus paclitaxel for advanced gastric cancer might yield a stronger antitumor effect. The objective of this study was to determine the dose-limiting toxicity (DLT), the maximum tolerated dose (MTD), the recommended dose (RD), and the preliminary antitumor activity of S-1 and cisplatin plus paclitaxel for advanced gastric cancer. Methods: Paclitaxel was administered on day 1. A fixed dose of S-1 (70 mg/m 2 /day) was orally administered for 14 consecutive days from day 1, and a 24-h infusion of a fixed dose of cisplatin (60 mg/m 2 ) was administered on day 14 of every 28-day cycle. Four dose escalation levels of paclitaxcel were studied (120, 140, 160, and 180 mg/m 2 ). The DLT was defined as any of the following: grade 3 neutropenia lasting more than 5 days, grade 4 hematological toxicity, grade 3 non-hematological toxicity, or treatment delay of greater than 2 weeks as a result of toxicity. Results: Twenty patients were enrolled. Hematological and non- hematological toxicity of over grade 2 was not observed at dose level 1 and 2. Three patients started at dose level 3. One developed grade 3 neutropenia for 5 days following by grade 2 neutropenia lasted more than 10 days. Five more patients were added at this level. The treatment was delayed over 2 weeks in 1 out of 8 patients. Three patients started at dose level 4. One developed grade 3 neutropenia and needed longer than 14 days to recover. Three patients added this level. In total, at dose level 4 the treatment was delayed over 2 weeks in 3 out of 6 patients as a result of neutropenia. We considered level 4 is the MTD and the RD of paclitaxcel was 160 mg/m 2 (dose level 3). The overall response rate was 75%. Conclusions: Triple combination chemotherapy consisting of S-1, cisplatin, and paclitaxel showed a tolerable dose of adverse reactions and favorable antitumor activity for gastric cancer. No significant financial relationships to disclose.
A dose-escalating and pharmacologic study of bortezomib in adult cancer patients with impaired renal function
Authors: D. Mulkerin, S. Remick, R. Ramanathan, A. Hamilton, C. Takimoto, A. Davies, P. Ivy, M. Karol, J. Kolesar, J. Wright
Journal: Journal of Clinical Oncology (2006)

2032 Background: Bortezomib is a highly selective and reversible inhibitor of the proteasome with activity in multiple myeloma and other malignancies. Patients (pts) with renal impairment have been treated in previous trials, but there has not been a systematic investigation into the effects of renal dysfunction on dosing. Study objectives were to characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of bortezomib, and to determine the maximum tolerated dose (MTD) in adults with advanced malignancy and renal insufficiency ranging in severity from mild to dialysis dependence. Methods: Fifty-one pts have received intravenous bortezomib at 0.7 mg/m 2 up to the approved dose of 1.3 mg/m 2 on days 1,4, 8, and 11 every 3 weeks. Pts were stratified by 24-hour creatinine clearance (CrCL) normalized to a body surface area of 1.73 m 2 into five cohorts per the table . Doses were escalated in cohorts of three pts in groups B-E. Blood samples were assayed for bortezomib concentration, as well as the PD endpoint of 20S inhibition. Results: Escalation of bortezomib doses to 1.3 mg/m 2 was well tolerated in all groups with CrCL ≥ 20 mL/min/1.73 m 2 . There has been only one instance of dose limiting toxicity (group C at 1.3 mg/m 2 ) which did not prevent successful completion of this cohort. No patients discontinued therapy due to renal deterioration. Doses of 0.7 mg/m 2 were tolerable in Group D patients (CrCL&lt; 20 mL/min/1.73 m 2 ). Five dialysis pts have been treated; 3 at 0.7 mg/m 2 , and 2 at 1.0 mg/m 2 . All tolerated therapy well, and accrual to Groups D and E continues. PK and PD assays are underway and the analysis will be reported in full. Conclusions: This study is the first comprehensive evaluation of bortezomib in pts with various degrees of renal insufficiency including dialysis dependence. Bortezemib at the approved dose of 1.3 mg/m 2 on this schedule is well tolerated by pts with CrCL ≥ 20 mL/min/1.73 m 2 . Results of this trial will allow for dosing recommendations for bortezomib use in pts with renal insufficiency. [Table: see text] [Table: see text]
<i>In vivo</i>confocal microscopy efficacy assessment of daylight photodynamic therapy in actinic keratosis patients
Authors: S.M. Seyed Jafari, T. Timchik, R.E. Hunger
Journal: British Journal of Dermatology (2016)

Reflectance confocal microscopy (RCM) is a noninvasive diagnostic technique with an acceptable sensitivity and specificity for actinic keratosis (AK).We evaluated efficacy of daylight photodynamic therapy (DL-PDT) in patients with AK using a new RCM atypia scoring system.All patients with AK lesions (Grade I-II) were included in our study (2012-15). Baseline clinical, dermoscopy and RCM evaluations were followed by DL-PDT. In the first follow-up, clinical examination, dermoscopy and RCM imaging of the treated area were carried out. Atypia scoring and cell size measurements were used to compare before and after RCM images.From 40 lesions (20 patients with mean age of 75·5 years), complete resolution and partial response of the actinic damage was detected in 80% and 17·5% of lesions, respectively. No cellular atypia was seen in the follow-up RCM images of 57·5% of lesions (n = 23), while in 40% of lesions (n = 16) minimal changes to the honeycomb pattern of the epidermis were seen in the follow-up RCM images (atypia score 1). Only one lesion showed minimal or no clinical response, and a persistent moderate amount of atypia in RCM. Furthermore, atypia score and mean cell size decreased significantly in the follow-up DL-PDT RCM images (P < 0·001, P = 0·001, respectively).RCM features of actinic damage at cellular level have been shown to correlate well with the results of a clinical assessment of AK lesions. This study confirms that in vivo RCM technology might be an additional technique to monitor the efficacy of DL-PDT for AK.
Fertility Preservation in Patients With Breast Cancer: Necessity, Methods, and Safety
Authors: Adrienne G. Waks, Ann H. Partridge
Journal: Journal of the National Comprehensive Cancer Network (2016)

As treatment paradigms improve and young women live longer after a breast cancer diagnosis, there is an increasing need to define the fertility-related problems that premenopausal women with breast cancer face, and, more importantly, to find solutions. This article discusses what is known regarding fertility risks associated with standard breast cancer treatment regimens and limitations of that information. We outline established and emerging techniques for fertility preservation, including recent developments surrounding the controversial utility of gonadotropin-releasing hormone agonists through chemotherapy, and review available data on the safety of pregnancy in breast cancer survivors. We highlight opportunities for further investigation, and contextualize fertility-related concerns in the modern treatment landscape. Above all, we stress the importance of this topic in a patient-centered approach to breast cancer care for young women.
Trauma and posttraumatic stress disorder in subjects with anxiety disorders
Authors: E J Fierman, M F Hunt, L A Pratt, M G Warshaw, K A Yonkers, L G Peterson, T M Epstein-Kaye, H S Norton
Journal: American Journal of Psychiatry (1993)

Trauma histories were obtained from 711 subjects in a large study of anxiety disorders, with the intent of determining the prevalence and nature of psychological trauma in this group. Twenty-seven percent of subjects reported significant trauma; 35% of these (10% of all subjects) met DSM-II-R criteria for posttraumatic stress disorder (PTSD). Subjects reporting sexual trauma were significantly more likely to have PTSD. The rate of PTSD was not higher in subjects with panic disorder than in those with other anxiety disorders.
A Trait-Based Approach to Advance Coral Reef Science
Authors: Joshua S. Madin, Mia O. Hoogenboom, Sean R. Connolly, Emily S. Darling, Daniel S. Falster, Danwei Huang, Sally A. Keith, Toni Mizerek, John M. Pandolfi, Hollie M. Putnam, Andrew H. Baird
Journal: Trends in Ecology & Evolution (2016)
Negative Studies in Cancer Research
Authors: Scott F. Huntington, Cary P. Gross
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Abstract 18452: IKca Current Contributes to Ventricular Repolarization During Chronic, Not Short-term, Heart Failure
Authors: Ingrid M Bonilla, Victor P Long, Patrick Wright, Kent Mowrey, Jeanne Green, Pedro A Vargas-Pinto, Peter J Mohler, Cynthia A Carnes
Journal: Circulation (2013)

Heart failure (HF) is a chronic disease that develops over months to years. In HF, ventricular repolarization is prolonged. We tested the hypothesis that I KCa modulates repolarization only when ventricular repolarization reserve is reduced as occurs in chronic HF, but not short term HF. Methods: A tachypacing - induced HF canine model was used, and LV midwall myocytes were isolated from 1 and 4 month HF groups, and compared to normal controls. Action potential duration at 50 (APD50) and 90% (APD90) repolarization was measured before and after the application of 100nM apamin (I KCa blocker, n=5-9 per group). Adjacent tissue (n=4 per group) was collected to measure the proteins encoding cardiac I KCa (SK2 and SK3). Results: One and 4 month HF had similar severity of HF (LVFS: 19.00 ± 1.36 vs. 15.9 ± 2.45, respectively P=NS). APD50 or APD90 in 1 month HF was no different from controls. 4 Mo HF resulted in a significant (P&lt;0.05) APD90 prolongation compared to both control and 1 Mo HF groups, consistent with reduced repolarization reserve. Apamin significantly increased (P&lt;0.05) APD50 and APD90 only in the 4 Mo HF group. Similarly proarrhythmic repolarization instability (beat-to-beat variability) was evident after apamin in the 4 month, but not the 1 month HF group (p&lt;0.05). SK2 expression was unchanged between groups; SK3 was increased ~ 4 fold in both 1 month and 4 month HF group (P&lt;0.05 vs control). Conclusions: Changes in SK protein expression do not fully explain I KCa -induced repolarization modulation. Rather, I KCa inhibition prolongs repolarization only when repolarization reserve is decreased, as occurs in chronic HF. The safety of targeting I KCa in chronic HF needs to be carefully evaluated as I KCa inhibition may increase susceptibility to ventricular arrhythmias.
Abstract 19080: Peak Exercise Capacity is a Poor Indicator of Functional Capacity for Patients Supported by a Continuous Flow Left Ventricular Assist Device
Authors: Nadav Nahumi, Arthur R Garan, Nir Uriel, Jason Han, Kerry A Morrison, Sunu S Thomas, Melana Yuzefpolskaya, Paolo C Colombo, Ulrich P Jorde
Journal: Circulation (2013)

Introduction: Six minute walk distance (6MWD) has been shown to be linearly related to peak oxygen uptake (VO2) during maximal exercise for patients suffering from heart failure (HF); however, this relationship in patients supported by left ventricular assist devices (CF-LVAD) is not well understood. Hypothesis: CF-LVADs readily support sub-maximal exercise such as walking, but this improvement is not accompanied by increased maximal exercise capacity due to relatively fixed cardiac output assistance provided by the LVAD. Methods: Forty patients with HF and 29 patients supported by LVADs performed a 6-minute walk test and a maximal cardiopulmonary exercise test. Results: The peak VO2 was linearly correlated with 6MWD in both HF (r=0.58, p&lt;0.001) and LVAD patients (r=0.53, p=0.003). While the slopes were similar, b=0.025 and b=0.029 for CHF and LVAD, respectively, patients with HF had a greater peak VO2 than patients supported by LVADs who achieved the same 6MWD. CF-LVAD patients walked approximately 80 meters more than HF patients in a 6-minute walk test for any given peak VO2. Conclusions: For any given peak VO2, patients supported by LVAD may have a greater functional capacity than HF patients. Peak VO2 should not be used as an outcome variable in clinical trials assessing functional capacity after LVAD implantation.
Cytochrome P450 Allele <i>CYP3A7*1C</i> Associates with Adverse Outcomes in Chronic Lymphocytic Leukemia, Breast, and Lung Cancer
Authors: Nichola Johnson, Paolo De Ieso, Gabriele Migliorini, Nick Orr, Peter Broderick, Daniel Catovsky, Athena Matakidou, Timothy Eisen, Christy Goldsmith, Frank Dudbridge, Julian Peto, Isabel dos-Santos-Silva, Alan Ashworth, Gillian Ross, Richard S. Houlston, Olivia Fletcher
Journal: Cancer Research (2016)

Abstract CYP3A enzymes metabolize endogenous hormones and chemotherapeutic agents used to treat cancer, thereby potentially affecting drug effectiveness. Here, we refined the genetic basis underlying the functional effects of a CYP3A haplotype on urinary estrone glucuronide (E1G) levels and tested for an association between CYP3A genotype and outcome in patients with chronic lymphocytic leukemia (CLL), breast, or lung cancers. The most significantly associated SNP was rs45446698, an SNP that tags the CYP3A7*1C allele; this SNP was associated with a 54% decrease in urinary E1G levels. Genotyping this SNP in 1,008 breast cancer, 1,128 lung cancer, and 347 CLL patients, we found that rs45446698 was associated with breast cancer mortality (HR, 1.74; P = 0.03), all-cause mortality in lung cancer patients (HR, 1.43; P = 0.009), and CLL progression (HR, 1.62; P = 0.03). We also found borderline evidence of a statistical interaction between the CYP3A7*1C allele, treatment of patients with a cytotoxic agent that is a CYP3A substrate, and clinical outcome (Pinteraction = 0.06). The CYP3A7*1C allele, which results in adult expression of the fetal CYP3A7 gene, is likely to be the functional allele influencing levels of circulating endogenous sex hormones and outcome in these various malignancies. Further studies confirming these associations and determining the mechanism by which CYP3A7*1C influences outcome are required. One possibility is that standard chemotherapy regimens that include CYP3A substrates may not be optimal for the approximately 8% of cancer patients who are CYP3A7*1C carriers. Cancer Res; 76(6); 1485–93. ©2016 AACR.
Pharmacology in the Era of Targeted Therapies: The Case of PI3K Inhibitors
Authors: Eneda Toska, José Baselga
Journal: Clinical Cancer Research (2016)

The PI3K pathway is often aberrantly activated in estrogen receptor positive (ER(+)) breast cancer and therapies combining PI3K inhibitors and antiestrogens are under clinical development. Given that many PI3K inhibitors have substantial toxicities with continuous dosing and that alternate dosing schedules are equally active, further clinical exploration is warranted. Clin Cancer Res; 22(9); 2099-101. ©2016 AACRSee related article by Yang et al., p. 2250.
Lower-dose dexamethasone (Dex)/thalidomide (Thal) and zoledronic acid (ZOL) every 3 weeks in previously untreated multiple myeloma.
Authors: G. Teoh, Y. Chen, K. Kim, A. Srivastava, V. R. Pai, S. Yoon, C. Suh, Y. Kim
Journal: Journal of Clinical Oncology (2010)

e18524 Background: Although multiple myeloma (MM) is uncommon in Asia, Asian patients are often unable to tolerate full doses of Dex and/or Thal that typically result in very good partial (VGPR), near-complete (nCR) or complete response (CR) while maintaining CD34 stem cell counts. Preparative regimens achieving these responses prior to autologous hematopoietic stem cell transplantation correlate with improved outcomes in MM. Therefore, optimal regimens are needed; however, co-operative clinical studies in Asia are lacking. We investigated if q 3-week administration of ZOL (shown to exert anti-MM effects in preclinical studies) combined with low doses of Dex/Thal would be well tolerated in Asian patients and generate responses to treatment. Methods: In this co-operative multicenter phase II non-randomized single arm study in India, Singapore and Korea, previously untreated MM patients received up to 6 cycles of Dex (20 mg 1 to 4 times q wk), Thal (50 mg q wk to 100 mg q d), and ZOL (4 mg q 3 wk) (dtZ regimen). Response was graded using Bladé's criteria. Results: A total of 52 patients were enrolled, with ISS stage at study entry of I (15.4%), II (61.5%), or III (23.1%). Among 44 evaluable patients, the dtZ regimen resulted in an overall response rate of 89%: VGPR in 23 (52%), nCR in 7 (16%), CR in 8 (18%) patients and partial response in 1 (2%) patients. CD34 stem cell counts were not adversely affected. Most adverse events were manageable in the outpatient clinic. Sepsis was the most common grade 3-4 toxicity (11 patients); 8 patients developed bronchopneumonia and 3 developed gastrointestinal or urinary tract infections. One patient had suspected pulmonary embolism. There were 4 (9%) deaths (3 severe sepsis, 1 unknown cause). There were no reports of peripheral neuropathy, osteonecrosis of the jaw, or end-stage renal failure. Conclusions: Adding ZOL to low-dose Thal/Dex (dtZ) appears to be effective for Asian patients with newly diagnosed MM, but the Thal/Dex dose-reduction was insufficient to prevent infection risks. Therefore, further studies with lower-dose Dex are warranted. No significant financial relationships to disclose.
Cardiologist shortage prompts NHS trust to ask GPs to cut referrals
Authors: Ingrid Torjesen
Journal: BMJ (2016)

A prestigious teaching hospital has asked GPs in neighbouring clinical commissioning groups (CCGs) to send their cardiology patients elsewhere, as a severe shortage of consultants means that it cannot guarantee the safety of its services.

Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust, has only just over half the consultant cardiology workforce it needs. Just 3.5 whole time equivalent (WTE) cardiology consultants are in post at the hospital, and the trust said that its attempt to recruit a further three WTE doctors had been unsuccessful and that it has been unable to find locums to cover the posts temporarily.

Evelyn Barker, chief operating officer at Cambridge University Hospitals, and Tracy Dowling, chief operating officer at the local Cambridgeshire …
2D Shear Wave Elastography is not Superior to Transient Elastography in Difficult-to-Scan Patients: A Comparative Feasibility Study
Authors: Benjamin Staugaard, Janne Fuglsang Hansen, Belinda Klemmensen Mössner, Bjørn Stæhr Madsen, Aleksander Krag, Peer Brehm Christensen, Maja Thiele
Journal: Hepatology (2015)
CSIG-05THE UBIQUITIN SPECIFIC PEPTIDASE 15 (USP15) SUPPRESSES PROLIFERATION OF HUMAN GLIOBLASTOMA CELL LINES VIA STABILIZATION OF HECTD1 E3 LIGASE
Authors: Maria Oikonomaki, Monika Hegi
Journal: Neuro-Oncology (2015)

BACKGROUND: Ubiquitin Specific Peptidase 15 (USP15) emerged as a gene associated with genomic deletion in 25% of glioblastoma. USP15 is a de-ubiquitinase, removing ubiquitin moieties and thereby stabilizing proteins. Previously, USP15 has been suggested to have tumor suppressor function via its substrates APC and Caspase 3, but also oncogenic function, depending on the molecular and cellular context. METHODS: Glioblastoma cell lines with stable expression of wild-type USP15 or its catalytic mutant, and respective vector controls were established and used for functional analysis. Colony formation assay and soft agar assay were used to evaluate proliferation. Interacting partners were identified with mass spectroscopy. RESULTS: USP15 expression reduced colony formation and growth in soft agar by inhibiting cell cycle progression. In order to identify the molecular pathways in which USP15 is implicated we determined protein-binding partners in the glioblastoma cell line LN-229 by mass spectrometry. Eight new proteins interacting with USP15 were identified, including the HECTD1 E3 ligase. The murine homologue of Hectd1 promotes the APC-Axin interaction to negatively regulate the Wnt pathway. We could show that USP15 can interact and de-ubiquitinate and thereby stabilize HECTD1 in glioblastoma cell-lines. In accordance, depletion of USP15 led to a decrease of HECTD1. Functional analyses of HECTD1 in LN-229 pheno-copied the effect observed for USP15. Investigations aiming at uncovering the pathways that are affected by these two proteins provide some evidence that USP15 and HECTD1 attenuate the canonical WNT pathway. CONCLUSION: The data support a tumor suppressing function of USP15 in a subset of glioblastoma mediated by stabilization of HECTD1.
Effects of Standard Treatments for Ductal Carcinoma In Situ—Making Informed Choices
Authors: Lesley Fallowfield, Adele Francis, Alastair M. Thompson
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Original article: Potentiation of cisplatin by alpha-Interferon in advanced non-small cell lung cancer (NSCLC): A phase II study
Authors: A. Bowman, R.J. Fergussion, S.G. Allan, M.E. Stewart, A. Gregor, M.A. Combleet, A.P. Greening, G.K. Crompton, R.C.F. Leonard, J.F. Smyth
Journal: Annals of Oncology (1990)