tbuckley/cabot-search huggingface dataset:
A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis
Authors: Jaclyn N. Taroni, Casey S. Greene, Viktor Martyanov, Tammara A. Wood, Romy B. Christmann, Harrison W. Farber, Robert A. Lafyatis, Christopher P. Denton, Monique E. Hinchcliff, Patricia A. Pioli, J. Matthew Mahoney, Michael L. Whitfield
Journal: Genome Medicine (2017)

Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology. We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast the skin and lung microenvironments and to assess the functional role of the inflammatory and fibrotic genes in each organ. Lastly, we tested the expression of macrophage activation state-associated gene sets for enrichment in skin and lung using a Wilcoxon rank sum test. We identified a common pathogenic gene expression signature—an immune–fibrotic axis—indicative of pro-fibrotic macrophages (MØs) in multiple tissues (skin, lung, esophagus, and peripheral blood mononuclear cells) affected by SSc. While the co-expression of these genes is common to all tissues, the functional consequences of this upregulation differ by organ. We used this disease-associated signature to query tissue-specific functional genomic networks to identify common and tissue-specific pathologies of SSc and related conditions. In contrast to skin, in the lung-specific functional network we identify a distinct lung-resident MØ signature associated with lipid stimulation and alternative activation. In keeping with our network results, we find distinct MØ alternative activation transcriptional programs in SSc-associated PF lung and in the skin of patients with an “inflammatory” SSc gene expression signature. Our results suggest that the innate immune system is central to SSc disease processes but that subtle distinctions exist between tissues. Our approach provides a framework for examining molecular signatures of disease in fibrosis and autoimmune diseases and for leveraging publicly available data to understand common and tissue-specific disease processes in complex human diseases.
The efficacy of aprepitant for the patients receiving FOLFOXIRI and FOLFIRINOX: A phase II study.
Authors: Yukami Hiroki, Tetsuji Terazawa, Takahiro Miyamoto, Ken Asaishi, Fukutaro Shimamoto, Shin Kuwakado, Hitoshi Nishitani, Takayuki Kii, Masahiro Goto, Kazuhide Higuchi, Makoto Sanomura
Journal: Journal of Clinical Oncology (2017)

560 Background: Aprepitant (APR) showed the efficacy for the prevention of chemotherapy-induced nausea and vomiting (CINV) with highly emetogenic chemotherapy. The combination chemotherapies of moderately emetoegnic agents of oxaliplatin and irinotecan are classified as moderately emetogenic risk according to ASCO guideline, but showed severe vomiting and nausea. Methods: This phase II trial evaluated the efficacy of APR (day1;125mg, day2-3; 80mg) in patients receiving mFOLFOXIRI(oxaliplatin; 85 mg/m 2 , irinotecan; 150 mg/m 2 , leucovorin; 200 mg/m 2 , 5-FU infusional; 2400 mg/m 2 /46hour, every 2 weeks) and FOLFIRINOX (oxaliplatin; 85 mg/m 2 , irinotecan; 180 mg/m 2 , leucovorin;200 mg/m 2 , 5-FU bolus; 400 mg/m 2 , 5-FU infusional; 2400 mg/m 2 /46hour, every 2weeks). The primary objective was the complete vomiting inhibitation rate (CVIR) during first cycle. The null hypothesis and expectation of CVIR were 30% and 60% (one-sided α = 0.05, β = 1.0), so 23 patients were needed. CVIR was assessed according to MAT (MASCC Antiemesis Tool). Results: 25 patients were enrolled. The characteristics were as follows; median age (range), 65 (39-71); male/ female, 16/9; PS0/ 1, 11/ 14; mFOLFOXIRI/ FOLFIRINOX, 20/ 5; BMI &lt; 22/ 22 or more, 14/ 11; history of alcohol yes/ no, 11/ 14. The CVIR was 92% (95%CI: 74-99) and complete response (no vomiting and no rescue medication use) rate was 72% (95%CI: 51-88%). The toxicities (all grade/ grade 3 or 4) were as follows; nausea, 17/ 2; vomiting, 3/ 0; fatigue, 16/ 2; constipation, 6/ 0. Conclusions: APR was effective for CVIR. Further prevention of nausea is expected.
Bevacizumab and its impact on survival for patients receiving subsequent anti-EGFR therapy: Results from the South Australian metastatic colorectal cancer registry.
Authors: Timothy Jay Price, Christos Stelios Karapetis, Amitesh Chandra Roy, Robert Padbury, Guy Maddern, David Roder, Cynthia Piantadosi, Matthew E. Burge, Amanda Rose Townsend
Journal: Journal of Clinical Oncology (2017)

754 Background: Questions over the impact of 1st line bevacizumab on subsequent sensitivity to anti-EGFR therapy have been raised with authors hypothesizing that up-front anti-VEGF agent’s use influences biological changes that increase the risk of acquired resistance to subsequent EGFR inhibitors. Methods: Aretrospective cohort study was performed to compare the characteristics and survival of patients who were treated with an anti-EGFR therapy 2nd line and beyond by two groups defined by the 1st line therapy; 1. chemotherapy (chemo) plus bevacizumab (bev) and 2. chemo alone. Pearson chi test analysis was performed to determine whether receiving 1 st line bev was associated with worse OS. Results: 348 mCRC patients who received chemo with or without bev and then an anti-EGFR therapy were studied. Patient characteristics are summarised in table. The significant differences between group 1. Vs. 2. were as follows; median age, lower use of single agent FU, KRAS status not tested, and where BRAF MT status was known (11%); BRAF MT rate. Median OS for the 2 groups was 34.2 mths, and 28.2 mths respectively (p = 0.12). Conclusions: Survival was not significantly different between the two groups, and the trend was towards higher OS with chemo plus bev suggesting that in our registry population, bev administration in first line therapy with chemo did not lead to a worse outcome for those patients subsequently receiving anti-EGFR therapy. [Table: see text]
Phase I study of BYL719 and trastuzumab-MCC-DM1 (T-DM1) in HER2-positive metastatic breast cancer (MBC) patients with progression on trastuzumab and taxane-based therapy.
Authors: Sarika Jain
Journal: Journal of Clinical Oncology (2014)

TPS672 Background: Despite the considerable efficacy of trastuzumab, eventually all HER2-positive MBC patients develop resistance and disease progression. Upregulation of the PI3K pathway and oncogenic activating mutations of PIK3CA mutations have been implicated in trastuzumab resistance. Simultaneously targeting HER2 and PI3K pathways may allow for a more effective treatment option in this population. Methods: This investigator-initiated phase I, open-label, single arm study employs a dose-escalating 3+3 design to determine safety and efficacy of T-DM1 (an antibody-drug conjugate that incorporates the HER2-targeted properties of trastuzumab with a microtubule-inhibitory agent) in combination with an oral PI3K inhibitor BYL719 in patients with HER2-positive locally advanced or MBC whose disease has progressed on trastuzumab and taxane-based regimens in the metastatic setting or within 6 months in the adjuvant setting. Three to 6 patients are being enrolled in 3 successive cohorts with dose escalation of daily BYL719 (Cohort 1: 300 mg, Cohort 2: 350 mg, Cohort 3: 400 mg). T-DM1 is given at the FDA approved dose of 3.6 mg/kg every 3 weeks. At the maximum tolerated dose (MTD), an additional 10 patients will be enrolled to gain further knowledge on safety. The primary objectives are to determine safety, tolerability, feasibility, and MTD. The secondary objectives will evaluate pharmacokinetics of BYL719 and efficacy. Exploratory endpoints will examine alterations of the PIK3CA gene, decrease of PTEN expression and other Akt/mTOR downstream markers. This will be performed on archival metastatic tumor tissue or an optional baseline tissue biopsy and compared to optional tissue biopsy after 3 cycles of treatment. Clinical trial information: NCT02038010.
A phase II trial comparing pemetrexed with gefitinib as the second-line treatment of nonsquamous NSCLC patients with wild-type EGFR (CTONG0806).
Authors: Jinji Yang, Ying Cheng, Mingfang Zhao, Qing Zhou, Hong hong Yan, Li Zhang, Yong Song, Jianhua Chen, Weineng Feng, Chong-Rui Xu, Yi Long Wu
Journal: Journal of Clinical Oncology (2013)

8042 Background: Pemetrexed or gefitinib is one of the standard second-line treatments for advanced non-squamousNSCLC in East Asia. The CTONG 0806 a multi-center, randomized, controlled, open-label phase II trial was designed to explore the efficacy of pemetrexed versus gefitinib as the second-line treatment in advanced NSCLC patients without EGFR mutation. Methods: The patients with locally advanced or metastatic, non-squamous NSCLC previously treated with platinum-based chemotherapy and no EGFR mutation in exons 18-21 were enrolled. Patients were 1:1 randomized to receive either gefitinib 250 mg per oral every day (G arm) or pemetrexed 500 mg/m 2 iv day 1 with vitamin B12 and folic acid supplement every 21 days (P arm) until disease progression, unacceptable toxicity, or discontinuation of treatment due to other reason. The primary endpoint was progression-free survival (PFS). The secondary endpoints were 4-month and 6-month progression-free survival rate, overall survival (OS), objective response rate (ORR), quality of life using the FACT-L questionnaire and safety, EGFR and K-ras mutation status were evaluated and correlated with outcomes. Results: From Feb. 2009 to Aug. 2012, 157 evaluable patients were randomized (81 cases in G arm and 76 in P arm). Baseline age, gender, and ECOG performance status were balanced between arms. The primary endpoint of PFS was met with 1.6 months for G arm versus 4.8 months for P arm, the HR is 0.51 (95% CI 0.36~0.73, P&lt;0.001). Overall response rates were 14.7 % and 13.3 % (P=0.814) and DCR were 32.0% and 61.3% (P&lt;0.001) for G arm and P arm, respectively. OS data were not yet mature. More skin rash and diarrhoea were seen in G arm, but more fatigue and ALT increased in P arm. CTCAE grade 3 or 4 of AEs was 12.3% in G arm and 32.9% in P arm (p=0.002). The further analyses of efficacy evaluated by IRR and biomarkers analysis will be presented on the ground. Conclusions: CTONG0806 is the first trial to show significant improvements in PFS and DCR with pemetrexed compared with gefitinib in second-line setting for advanced NSCLC with EGFR wild type. Patients with EGFR wild type did not benefit from EGFR TKI gefitinb in second-line setting. Clinical trial information: NCT00891579.
Erythropoietin and Erythropoietin Receptor Expression in Early Stage Non-Small Cell Lung Cancer: Prognostic Significance.
Authors: Khalid Amin, Zishan A. Haroon, Seok J. Kim, Sufeng Li, Zahid N. Rabbani, Robin T. Vollmer, Xiaofei F. Wang, Michael J. Kelley, Murat O. Arcasoy
Journal: Blood (2005)
Erratum: Functional coupling of p38-induced up-regulation of BiP and activation of RNA-dependent protein kinasel-like endoplasmic reticulum kinase to drug resistance of dormant carcinoma cells (Cancer Research (February 1, 2006) 66 (1702-1711))
Authors: A. C. Ranganathan, L. Zhang, A. P. Adam, J. A. Aguirre-Ghiso
Journal: Cancer Research (2006)
Assessing Performance of Internal Medicine Residents
Authors: Paul A. Monach
Journal: JAMA (2017)

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
Characterization and identification of specific EGFR mutations in circulating tumor cells (CTCs) isolated from non-small cell lung cancer patients using antibody independent method, ApoStream.
Authors: Hai T. Tran, Vladislava O. Melnikova, Anne S. Tsao, Frank V. Fossella, Faye M. Johnson, Vassiliki Papadimitrakopoulou, Miguel Garza, Chris Neal, Dave Hasegawa, Amy Kruempel, Grant Wu, Katherine Richardson, Marcia E. Lewis, Benjamin Jr Legendre, Kenna Lynn Anderes, Darren W. Davis, John Heymach
Journal: Journal of Clinical Oncology (2013)

11044 Background: A variety of methods for isolation of CTCs of epithelial origin are available; most employ antibodies to epithelial cell adhesion molecule (EpCAM). Using classic phenotypic definition, a CTC is nucleated, cytokeratin CK(+), CD45(-) cell. However, some CTCs may elude capture as they originate from primary tumor cells which have undergone epithelial-mesenchymal transition (EMT). We report here the use of ApoStream, a novel dielectrophoresis field-flow-assisted, antibody-free method to isolate CTCs from blood. Methods: Blood was collected from consented NSCLC patients and processed using ApoStrea. For CTC enumeration comparison, CellSearch FDA-approved kit was used. Isolated cells were evaluated with multiplexed immunofluorescent assay and laser scanning cytometry analysis were applied to identify multiple combinations of positive and/or negative staining for CK/CD45/DAPI and EpCam. To determine specific EGFR mutations from captured CTCs, samples were analyzed using Improved and Complete Enrichment with CO-amplification at Lower Denaturation temperature (ICE COLD-PCR). Results: Blood samples from 32 NSCLC patients and 3 healthy volunteers were processed. ApoStream isolated 0 to 65 CK(+)/CD45(-) CTCs(n=32) and CellSearch isolated 0 to 13 EpCAM(+)/CK(+)/CD45(-) CTCs(n=7). Additionally, ApoStream™ recovered 37-3536 CK(-)/CD45(-) and 4-10702 CK(+)/CD45(+) cells. EpCAM expression was detected in 7-100% of CK(+)/CD45(-) and 0-5% of CK(-)/CD45(-) cells, and 18-100% of CK(+)/CD45(+) cells. EGFR mutations [exon 19 deletion and exon 21 L858R] were determined and found to be concordant when compared to tumor tissue analysis by Sanger sequencing. Conclusions: The ApoStream platform enriched EpCAM(+) and EpCAM(-) CTCs from the blood of NSCLC patients demonstrating utility in recovering cancer cells with multiple phenotypes. From recovered CTCs, detection of EGFR mutations was possible indicating the clinical relevance and potential utility of CTCs as an alternative to tissue biopsy. Complete mutation analysis will be presented.
Online social network use among parents of young childhood cancer survivors.
Authors: Justin Gregory Wilford, Kathryn Osann, Lari B. Wenzel
Journal: Journal of Clinical Oncology (2017)

82 Background: Online social networks (OSNs) have emerged in the past decade as potentially powerful tools for health information sharing and health behavior change. According to a recent study by the Pew Research Center, 75% of all parents are active on OSNs. Given the high level of need for childhood cancer survivorship health education and preventive health behavior change, OSNs represent key resources for parents to engage with experts and peers over survivorship health. Methods: A cross-sectional survey of 114 parents of young and adolescent ( &lt; 13 years) childhood cancer survivors was used to examine parent OSN use in specific platforms. Recruitment was conducted through online social support groups of two childhood cancer non-profits that focus on parent support. The novel online survey investigated OSN frequency of use, history of making new friends in OSNs, and whether OSNs were “good for sharing and receiving reliable and high quality information on diet, physical activity, and other healthy behaviors.” Results: Parents reported high levels of OSN use with 80% reporting daily use. Facebook was the most commonly used OSN by a wide margin. Seventy-eight percent of parents reported using it every day. The next most used OSN was Instagram (15%). Parents reported making new friends on Facebook (86%), followed by Instagram (22%) and Twitter (10%). Among parents who have used the respective OSNs, several were endorsed as being “good” or “extremely good” for sharing survivorship-related preventive health information. Facebook was endorsed by 76% of its users, Twitter and Pinterest by 59%, Google+ by 52%, and Instagram by 40%. None of the demographic variables collected predicted parent OSN use or perception. There was a strong association between parents using OSNs daily and their reporting having made new friends on OSNs (p &lt; .000). Conclusions: Parents of young childhood cancer survivors recruited from online support groups report high levels of OSN use and making new friends through OSNs, and find OSNs potentially good sources for sharing and receiving survivorship-related health information. OSNs in general, and Facebook in particular, represent promising avenues for childhood cancer survivorship health information dissemination.
Predicting nonsentinel lymph node metastases using established nomograms among patients with breast cancer after primary systemic therapy (PST): The transSENTINA substudy.
Authors: Cornelia Liedtke, Dennis Goerlich, Kimberly J. Van Zee, Jelka Korndoerfer, Ingo Bauerfeind, Tanja N Fehm, Barbara Fleige, Gisela Helms, Annette Lebeau, Marion Mai, Annette Staebler, Gunter Von Minckwitz, Michael Untch, Thorsten Kühn
Journal: Journal of Clinical Oncology (2013)

1020 Background: Recent studies such as the SENTINA trial suggest that performing SLNB in patients with a cN1 status before but converting to a ycN0 status through PST result more often in a false-negative evaluation of LN status compared to SLNB at primary surgery. Therefore, there is a need to predict non-SLN status after PST and tailor axillary staging procedures. We investigated the accuracy of established nomograms to predict non-SLN metastases at primary surgery in patients after PST. Methods: The SENTINA trial is a 4-arm prospective multicenter cohort study evaluating an algorithm for the timing of a standardized SLNB in patients undergoing PST. 1,737 pts. from 104 institutions were categorized into four treatment arms according to the clinical axillary staging (including ultrasound examination) before and after chemotherapy. Patients in arm C with a cN1 status prior to PST converting to a ycN0 status but found to have a histologically positive SLN after PST were included. Several published nomograms predicting non-SLN status in patients with a positive SLN at primary surgery were applied (including the MSKCC-, Mayo-, Cambridge-, and Stanford-Nomogram, MDA-Score and Tenon-Score) and Area-under-the-Curve-(AUC)-values were calculated. Results:This subgroup comprised 592 patients. Among these, 74 patients had a positive SLN after PST and had all available data to run the nomograms. AUC-values were: MSKCC: 82.3 (95% confidence interval (95%CI) 72.6-91.9), Mayo: 71.8 (95%CI 60.1-83.5), Cambridge: 71.5 (95%CI 59.7-83.2), Stanford 70.6 (95%CI 59.7-83.2), MDA 70.7 (95%CI 59.0-82.5), and Tenon 73.1 (61.5-84.7). Conclusions: Analysis of the above nomograms in the post-neoadjuvant setting yielded AUC values comparable to those in the setting of primary surgery. Our results suggest that nomograms predicting non-SLN status in the setting of primary surgery (and particularly the MSKCC nomogram) may be used to avoid full axillary dissection in patients after PST.
Neurobiology of Disease
Authors: Charles M. Poser
Journal: JAMA (1990)

Starting approximately twenty years ago, neuroanatomy and neurophysiology appropriately were combined under the designation neurobiology. Unfortunately, at about the same time, neuropathology, as one of the basic sciences, began its steady downward trend so that at the present time, it is not usually included in neurobiology teaching. It may well be relevant to remember Derek Denny-Brown's remark, "The basic science of neurology is neuropathology." This book addresses medical students and physicians as well as graduate students and scientists in neurobiology; from its contents, it is clear that it is not designed for the experienced clinical or basic neuroscientist. The first of its two parts deals with functional and anatomic systems, the second with disease processes. As frequently occurs in multiauthored compendiums, there is great variability in style and quality. In most instances, however, the discussions are clear and the illustrations well chosen. An attractive feature consists of the presentation in
Impact of local intervention (surgery/radiation) in patients with metastatic renal cell carcinoma (MRCC) treated with tyrosine kinase inhibitors (TKIs) stratified by Heng criteria (HC).
Authors: Caroline Arden Merwarth, Asim Amin, Yimei Han, James Thomas Symanowski, Earle Frederick Burgess, Kris E Gaston, Stephen Boyd Riggs
Journal: Journal of Clinical Oncology (2015)

e15614 Background: Historical data from patients treated with interleukin-2 (IL2) suggest benefit for local intervention in selected cases. It is not clear if patients treated with TKIs would derive a similar benefit. HC predict for outcomes in patients with MRCC treated with TKIs. We assessed the impact of local intervention in patients with MRCC treated with TKIs stratified by HC. Methods: Retrospective analysis was carried out on patients with MRCC treated from 2000-2013 with IL2, TKI or both. Patients were stratified per HC into favorable, intermediate and poor risk groups. Patients were classified as unknown risk if complete information was not available. Outcomes were compared for patients who had been treated with TKIs and underwent local intervention with metastasectomy and/or stereotactic radiosurgery or not. Results: Of the 233 evaluable patients, 137 received systemic treatment and 96 received both systemic as well as local intervention. The median age was 56 yrs; 75% were male. Clear cell histology was confirmed in 77%. Of the 124 patients treated with IL2, 84 received subsequent TKI; 109 patients were treated with TKIs only. The 5-year overall survival (OS) and progression free survival (PFS) rates were significantly better for patients treated with systemic treatment plus local intervention compared to systemic treatment alone (OS 73% vs 49%, HR 0.35, 95% CI: 0.20-0.63; PFS 36% vs 18%, HR 0.59, 95% CI: 0.43-0.83). Benefit from local intervention progressively diminished from favorable to poor stratifying by Heng criteria. (Table.) Conclusions: Patients with MRCC who receive local intervention in addition to their systemic treatment may have improved OS and PFS compared to those who receive systemic treatment alone. HC may help select patients receiving TKIs suitable for local intervention. HR (CI)* OS PFS Heng Risk Number of patients in STLI Favorable n=20 10 0.17 (0.02, 1.46) 0.44 (0.11, 1.77) Intermediate n=72 29 0.26 (0.09, 0.74) 0.45 (0.24, 0.84) Poor n=41 16 0.62 (0.21, 1.87) 0.92 (0.44, 1.95) Unknown Risk n=60 25 0.34 (0.08, 1.38) 0.60 (0.31, 1.14) Total n=193 80 0.33 (0.18, 0.60) 0.58 (0.41, 0.83) *STLI vs ST.