tbuckley/cabot-search huggingface dataset:
Phase 1 pharmacokinetic and pharmacodynamic study of the histone deacetylase inhibitor MS-275 in combination with 13-cis retinoic acid in patients with advanced solid tumors
Authors: R. Pili, M. Rudek, S. Altiok, D. Qian, M. Zhao, R. Donehower, A. Anderson, M. Halter, H. McFarland, J. Zwiebel, M. Carducci
Journal: Journal of Clinical Oncology (2006)

3055 Background: Preclinical studies suggest that histone deacetylase (HDAC) inhibitors may restore tumor sensitivity to retinoids. The objective of this study was to determine the maximum-tolerated dose (MTD), the dose-limiting toxicity (DLT), and the pharmacokinetic (PK)/pharmacodynamic (PD) profiles of the HDAC inhibitor MS-275 in combination with 13-cis retinoic acid (CRA). Methods: Patients (pts) with advanced solid tumors were treated with MS-275 orally once weekly and CRA orally twice daily x 3 weeks every 4 weeks. The starting dose for MS-275 was 4 mg/m 2 and the dose was escalated based on toxicity assessments. The fixed dose for CRA was 1 mg/kg/day. PK concentrations of MS-275 and CRA were determined by LC/MS/MS. Western Blot analysis on peripheral-blood mononuclear cells (PBMCs) and tumor samples (when feasible) were performed to evaluate target inhibition. Results: To date thirteen pts have been enrolled. Tumor types include prostate (4 pts), bladder and renal cell (2 pts), and others. The MTD was exceeded at the 5 mg/m 2 dose level (G3 hyponatremia, neutropenia and anemia). Fatigue (G1 or G2) is a common side effect. MS-275 peak concentrations were 141.6±75.7ng/mL at 4mg/m 2 and 139.5±30.9 ng/mL at 5mg/m 2 . MS-275 half-life and clearance were 108.2±47.9h and 9.4±6.0L/h/m 2 , which is consistent with prior reports for MS-275 as single agent. Median CRA steady-state trough levels were 182.4 ng/mL. The MTD was 4 mg/m 2 MS-275 and 1 mg/kg CRA. Five pts remained on treatment for ≥ 4 months including pts with prostate cancer (3), pancreatic cancer (6 months) and a pt with renal cell carcinoma (12 months) who presented a partial response in the lungs. Histones isolated from PBMCs showed transient but consistent protein acetylation post-therapy. Tumor biopsy of a liver lesion from prostate carcinoma revealed post-therapy induced histone acetylation and decreased phosphorylated ERK and STAT3 protein expression consistent with HDAC inhibitory activity. Conclusions: Combination of MS-275 with CRA is reasonably well tolerated and 4 mg/m 2 is the Phase II recommended dose for MS-275 in combination with CRA. Tumor response and PD data suggest clinical and biological activity for this combination strategy. [Table: see text]
Uptake of Active Surveillance for Very-Low-Risk Prostate Cancer in Sweden
Authors: Stacy Loeb, Yasin Folkvaljon, Caitlin Curnyn, David Robinson, Ola Bratt, Pär Stattin
Journal: JAMA Oncology (2016)

<h3>Importance</h3> Active surveillance is an important option to reduce prostate cancer overtreatment, but it remains underutilized in many countries. Models from the United States show that greater use of active surveillance is important for prostate cancer screening to be cost-effective. <h3>Objectives</h3> To perform an up-to-date, nationwide, population-based study on use of active surveillance for localized prostate cancer in Sweden. <h3>Design, Setting, and Participants</h3> Cross-sectional study in the National Prostate Cancer Register (NPCR) of Sweden from 2009 through 2014. The NPCR has data on 98% of prostate cancers diagnosed in Sweden and has comprehensive linkages to other nationwide databases. Overall, 32 518 men with a median age of 67 years were diagnosed with favorable-risk prostate cancer, including 4693, 15 403, and 17 115 men with very-low-risk (subset of the low-risk group) (clinical stage, T1c; Gleason score, ≤6; prostate-specific antigen [PSA], &lt;10 ng/mL; PSA density &lt;0.15 ng/mL/cm<sup>3</sup>; and &lt;8-mm total cancer length in ≤4 positive biopsy cores), low-risk (including all men in the very-low-risk group) (T1-T2; Gleason score, ≤6; and PSA, &lt;10 ng/mL), and intermediate-risk disease (T1-T2 with Gleason score, 7 and/or PSA, 10-20 ng/mL). <h3>Exposures</h3> Diagnosis with favorable-risk prostate cancer. <h3>Main Outcomes and Measures</h3> Utilization of active surveillance. <h3>Results</h3> The use of active surveillance increased in men of all ages from 57% (380 of 665) to 91% (939 of 1027) for very-low-risk prostate cancer and from 40% (1159 of 2895) to 74% (1951 of 2644) for low-risk prostate cancer, with the strongest increase occurring from 2011 onward. Among men aged 50 to 59 years, 88% (211 of 240) with very-low-risk and 68% (351 of 518) with low-risk disease chose active surveillance in 2014. Use of active surveillance for intermediate-risk disease remained lower, 19% (561 of 3030) in 2014. <h3>Conclusions and Relevance</h3> Active surveillance has become the dominant management for low-risk prostate cancer among men in Sweden, with the highest rates yet reported and almost complete uptake for very-low-risk cancer. These data should serve as a benchmark to compare the use of active surveillance for favorable-risk disease around the world.
Safety of bevacizumab (Bv) therapy in combination with chemotherapy in subjects with non-small cell lung cancer (NSCLC) treated on ATLAS
Authors: J. Polikoff, J. D. Hainsworth, L. Fehrenbacher, S. Royer-Joo, Y. Mu, D. K. Strickland, V. A. Miller
Journal: Journal of Clinical Oncology (2008)

8079 Background: Although two randomized, phase III trials have combined Bv with carboplatin/paclitaxel or cisplatin/gemcitabine in patients with non-squamous NSCLC, there is little information for Bv in combination with other chemotherapy regimens. We report preliminary safety information from subjects treated with Bv in combination with carboplatin/paclitaxel (CP), carboplatin/gemcitabine (CG), and carboplatin/docetaxel (CD). Methods: Subjects received up to 4 cycles of chemotherapy (as determined by the investigator) + Bv 15 mg/kg every 3 weeks (chemotherapy phase), followed by Bv ± erlotinib to progressive disease (PD). Eligibility included advanced or metastatic non-squamous (or predominantly squamous cell histology with peripheral and/or extrathoracic lesions) NSCLC and no recent arterial thromboembolic events (ATE), gastrointestinal (GI) perforation, or hemoptysis. Subjects on low molecular weight heparin or with previously treated brain metastases were eligible. Specific safety events and all adverse events (AE) leading to study therapy interruption or discontinuation were collected. Results: Specific safety events for 598 subjects enrolled from 01/06–08/07 and reported during the chemotherapy phase are listed in the table. Conclusion: To date, among 598 subjects analyzed, there have been no unexpected safety events with Bv in combination with CP, CG, or CD. Furthermore, the safety profile of the combinations appears similar for severe specific adverse events, although CD has a higher rate of AE’s leading to discontinuation. The study continues to accrue subjects (to 1,150 subjects) and additional safety data with additional exposure and follow up will be presented. Regimen Bv + CP (N=303) Bv + CG (N=183) Bv + CD (N=112) Median age, years (range) 63 (33–84) 67 (36–88) 65 (23–82) Gender, % Male 51 51 55 Female 48 49 45 ECOG PS, % 0 43 44 43 1 55 56 57 Stage, % IIIb 11 10 6 IV 85 82 89 Recurrent 2 7 4 Mean Bv exposure (number of doses) 3.5 3.5 3.2 Grade ≥3 AEs, n (%) GI perforations 3 (<1) 0 2(1.8) ATE 6 (2) 2 (1) 1 (<1) CHF 2 (<1) 1 (<1) 1 (<1) Hypertension 13 (4.3) 9 (4.9) 3 (2.7) Overall hemorrhage (all grades), n (%) 7 (2.3) 9 (4.9) 9 (8.0) Grade≥2 Pulmonary hemorrhage 2 (<1) 1 (<1) 2 (1.8) Grade≥2 CNS hemorrhage 1 (<1) 1 (<1) 1 (<1) AEs leading to discontinuation (all grades), n (%) 36 (11.9) 23 (12.6) 20 (17.9) AEs=Adverse events; ATE=arterial thromboembolic events; CHF=Congestive Heart Failure; CNS=Central nervous system. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology Genentech™ BioOncology Genentech™ BioOncology Genentech™ BioOncology
Parallel Evolution of Cold Tolerance Within <i>Drosophila melanogaster</i>
Authors: John E. Pool, Dylan T. Braun, Justin B. Lack
Journal: Molecular Biology and Evolution (2016)

Drosophila melanogaster originated in tropical Africa before expanding into strikingly different temperate climates in Eurasia and beyond. Here, we find elevated cold tolerance in three distinct geographic regions: beyond the well-studied non-African case, we show that populations from the highlands of Ethiopia and South Africa have significantly increased cold tolerance as well. We observe greater cold tolerance in outbred versus inbred flies, but only in populations with higher inversion frequencies. Each cold-adapted population shows lower inversion frequencies than a closely-related warm-adapted population, suggesting that inversion frequencies may decrease with altitude in addition to latitude. Using the FST-based “Population Branch Excess” statistic (PBE), we found only limited evidence for parallel genetic differentiation at the scale of ∼4 kb windows, specifically between Ethiopian and South African cold-adapted populations. And yet, when we looked for single nucleotide polymorphisms (SNPs) with codirectional frequency change in two or three cold-adapted populations, strong genomic enrichments were observed from all comparisons. These findings could reflect an important role for selection on standing genetic variation leading to “soft sweeps”. One SNP showed sufficient codirectional frequency change in all cold-adapted populations to achieve experiment-wide significance: an intronic variant in the synaptic gene Prosap. Another codirectional outlier SNP, at senseless-2, had a strong association with our cold trait measurements, but in the opposite direction as predicted. More generally, proteins involved in neurotransmission were enriched as potential targets of parallel adaptation. The ability to study cold tolerance evolution in a parallel framework will enhance this classic study system for climate adaptation.
Comparison of Dopamine Transporter SPECT and 123I-MIBG Myocardial Scintigraphy to Assess Clinical Severity in Patients With Parkinson Disease
Authors: Nanami Okano, Mamoru Niitsu, Junji Tanaka, Takahiro Sasaki, Kazushi Takahashi, Nobuo Araki, Toshimasa Yamamoto, Shintaro Nakano, Shigeyuki Nishimura, Takaaki Senbonmatsu, Ichiro Matsunari
Journal: Clinical Nuclear Medicine (2016)

The aim of our study was to evaluate the use of dopamine transporter (DAT) SPECT and I-MIBG myocardial scintigraphy to determine the clinical severity of Parkinson disease (PD), with a focus on motor impairments affecting activities of daily living (ADLs).Data for 65 consecutive PD patients who underwent both DAT and MIBG imaging were reviewed. Associations between imaging variables and Hoehn and Yahr (H&Y) staging or self-supportive care ratings were investigated. Univariate and multivariate regression analyses were performed to determine the factors associated with ADLs.After applying the exclusion criteria, 45 patients were analyzed (age, 73.1 ± 9.3 years; 23 males; H&Y stage 1: n = 12, stage 2: n = 14, stage 3: n = 10, stage 4: n = 5, and stage 5: n = 4; self-supportive care rating-dependent ADLs: n = 29). Dopamine transporter variables were significantly associated with the clinical severity of PD as assessed by H&Y staging, whereas MIBG variables were not. Dopamine transporter variables gradually decreased throughout progressive stages, whereas the MIBG variables changed only in the advanced stages. In a multivariate analysis including clinical and imaging variables, both lower DAT and MIBG uptakes were significantly associated with dependent ADL status (P = 0.028 and 0.034, respectively).In patients with PD, DAT SPECT and MIBG myocardial scintigraphy were associated with ADL status; DAT SPECT was a stronger indicator of severity than MIBG myocardial scintigraphy in the early and middle stages.
Is Ureaplasma spp. the leading causative agent of acute chorioamnionitis in women with preterm birth?
Authors: J. Kikhney, D. von Schöning, I. Steding, J. Schulze, A. Petrich, A. Hiergeist, U. Reischl, A. Moter, A. Thomas
Journal: Clinical Microbiology and Infection (2016)
Palliative Care–Led Meetings for Families of ICU Patients
Authors: Allison M. Remy, Kenneth E. Remy, Joan L. Rosenbaum
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Retrospective Evaluation of Incidence and Prognostic Factors for Stenotrophomonas Maltophilia Bacteremia Following Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Kaito Harada, Noritaka Sekiya, Shugo Sasaki, Satoshi Kaito, Shuhei Kurosawa, Yutaro Hino, Masahiro Sakaguchi, Keita Yamamoto, Shuntaro Ikegawa, Kosuke Yoshioka, Kyoko Watakabe, Daisuke Watanabe, Yasushi Senoo, Yuho Najima, Takeshi Hagino, Takeshi Kobayashi, Noriko Doki, Kazuhiko Kakihana, Hisashi Sakamaki, Kazuteru Ohashi
Journal: Blood (2015)
Geriatric day hospitals.
Authors: J George
Journal: BMJ (1971)

gastric mucosa is an important predisposing factor.But in Jones and his colleagues' cases the emphasis was on duodenal ulceration, and a purely ischaemic aetiology seems unlikely.A common factor may enter into the causation of both lesions.The severity of atheroma is related to cigarette smoking,6 and the evidence points to a relationship between peptic ulceration and smoking.7 Unfortunately there are no data on the smoking habits of Jones and his colleagues' patients.Be this as it may, it is important to know of the association lest haematemesis in a patient with an abdominal aneurysm is automatically attributed to its incipient rupture.
Estrogen promotes megakaryocyte polyploidization via estrogen receptor beta-mediated transcription of GATA1
Authors: C Du, Y Xu, K Yang, S Chen, X Wang, S Wang, C Wang, M Shen, F Chen, M Chen, D Zeng, F Li, T Wang, F Wang, J Zhao, G Ai, T Cheng, Y Su, J Wang
Journal: Leukemia (2016)
<i>Mafb</i> lineage tracing to distinguish macrophages from other immune lineages reveals dual identity of Langerhans cells
Authors: Xiaodi Wu, Carlos G. Briseño, Vivek Durai, Jörn C. Albring, Malay Haldar, Prachi Bagadia, Ki-Wook Kim, Gwendalyn J. Randolph, Theresa L. Murphy, Kenneth M. Murphy
Journal: The Journal of Experimental Medicine (2016)

Current systems for conditional gene deletion within mouse macrophage lineages are limited by ectopic activity or low efficiency. In this study, we generated a Mafb-driven Cre strain to determine whether any dendritic cells (DCs) identified by Zbtb46-GFP expression originate from a Mafb-expressing population. Lineage tracing distinguished macrophages from classical DCs, neutrophils, and B cells in all organs examined. At steady state, Langerhans cells (LCs) were lineage traced but also expressed Zbtb46-GFP, a phenotype not observed in any other population. After exposure to house dust mite antigen, Zbtb46-negative CD64+ inflammatory cells infiltrating the lung were substantially lineage traced, but Zbtb46-positive CD64− cells were not. These results provide new evidence for the unique identity of LCs and challenge the notion that some inflammatory cells are a population of monocyte-derived DCs.
Expression of a cancer associated isoform of PCNA in breast cancer has implications as a potential biomarker
Authors: L. H. Malkas, L. A. Schnaper, B. Herbert, W. Abdel-Aziz, Y. Liu, L. E. Dobrolecki, D. Hoelz, B. Agarwal, S. Badve, R. J. Goulet, R. J. Hickey
Journal: Journal of Clinical Oncology (2007)

21069 Background: We have identified a novel cancer associated isoform of the protein, proliferating cell nuclear antigen (PCNA), termed (caPCNA), and demonstrated that this isoform arises through a direct protein post-translational modification, and not via genetic mutation or RNA splice variation. Our results suggest that caPCNA has the potential to serve as a highly effective and unique marker for identifying malignant breast cancer cells. Methods: This assertion is based on our proteomic-based analyses of more than 60 malignant and non- malignant breast cell lines and tissues. Commercially available antibodies against PCNA cannot distinguish between the different isoforms of PCNA present in malignant and non-malignant breast cells and cannot be used clinically to differentiate between normal and malignant breast tissue. However, we have recently developed a rabbit polyclonal antibody, (caPCNAab), which specifically recognizes only the caPCNA isoform expressed by malignant human breast cells. Results: Using this antibody we clearly show that caPCNA is expressed only in malignant breast cells and tissues, and can be found in early disease. caPCNA expression in tissues was quantified as average staining intensity X average percentage of cells stained. Using this criterion the following data were obtained: 10 cases of normal breast tissue (reduction mammoplasty) gave a total score of 1%; 35 cases of normal breast tissue adjacent to malignancy scored as 4%; 30 cases of DCIS scored as 90%; and 55 cases of invasive breast carcinoma scored as 120%. The five cases of ADH examined thus far were shown to score similar to that of normal breast tissue. Conclusions: The implication of these data is that the development of a caPCNAab-based IHC stain could potentially be used to reliably stain only in situ or invasive carcinoma, and distinguish genuinely benign lesions (e.g., ADH) from carcinoma, (e.g., DCIS) allowing definitive diagnosis in such cases where a limited amount of an atypical lesion prevents definitive diagnosis on routine H/E stained sections alone. For the patient population, this could result in a marked decrease in the need for either a repeat core biopsy or an excisional biopsy due to an inconclusive initial diagnosis. No significant financial relationships to disclose.
A clinical review of 33 cases of breast phyllodes tumor over the last 20 years
Authors: M. S. Lenhard, S. Kahlert, I. Himsl, N. Ditsch, M. Untch, K. Friese, I. Bauerfeind
Journal: Journal of Clinical Oncology (2006)

10629 Background: The “Cystosarcoma phyllodes” of the breast is a rare entity which accounts for 0.5 % of all breast neoplasms. The diagnosis should be considered in all rapidly growing breast nodules. We reviewed all cases of this rare disease that presented at our hospital in the last 20 years. Methods: The data of 5270 patients with primary breast neoplasms treated in our department between 1984 and 2005 were retrospectively analyzed for the histopathologic diagnosis of a cystosarcoma phyllodes. Results: 33 patients with cystosarcoma phyllodes of the breast could be identified. The median age at diagnosis was 47 years. Median follow up was 86 months. The tumors were classified histologically into benign (40%), borderline (27%) and malignant tumors (33%) based on standardized criteria; 3 tumors were unclassified. Surgery was conducted as a breast conserving (58%) or radical operation (mastectomy) (42%). Median tumor size was 7.1 cm, and no lymph node infiltration was found in the 8 patients who received axillary lymph node dissection. Local recurrence occured in 8 patients (26%). 75% (6/8) of the patients with a local recurrence had been treated with a breast conserving surgery. In patients with the diagnosis of a malignant phyllodes tumor we observed a recurrence rate of 40% (4/10), in those with borderline tumors of 25% (2/8) whereas those with benign phylloides tumor had a local relapse rate of 8% (1/12). Distant metastases were seen in 4 patients (12%) with a malignant phyllodes tumor. All patients with distant metastases in the follow up had been treated radically at primary diagnosis. Neither regarding age at primary diagnosis nor in tumor size there was a significant difference between patients with local recurrence or metastasic spread and those without (p = 0.284 tumor size, p = 0.739 for age, Wilcoxon-W). Conclusions: We recommend local excision with appropiate surgical margins in all patients if the tumor-to-breast ratio is sufficient for good cosmesis. Based on our data, routine axillary lymph node dissection is not recommended. Patients with a malignant tumor are at higher risk for local recurrence and metastasic spread. Therefore, the histopathologic classification seems to be the strongest prognostic factor in this disease. No significant financial relationships to disclose.
Urinary Excretion of Epinephrine and Dopamine Correlates with Efficiency of G-CSF Mobilized Stem Cells in Patients with AL Amyloidosis
Authors: Heather Landau, Hani Hassoun, James E. Hoffman, Christina Bello, Elizabeth Hoover, Elyn Riedel, Paul S. Frenette, Raymond L. Comenzo
Journal: Blood (2011)
Colorectal Cancer Screening—Reply
Authors: Jennifer S. Lin, Leslie A. Perdue, Elizabeth O’Connor
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
GW26-e4560 Using implantable cardioversion defibrillator to treat those patients with malignant arrhythmia (with 4 cases report)
Authors: Dongming Xie, Yihong Yang, Xiangzhong Liao, Zhanglin Yan, Xifeng Zhou, Gulao Zhang, Jiayuan Ling, Jinhai Zhu, Bei Wang, Ping Lai, Kun Xiao
Journal: Journal of the American College of Cardiology (2015)