tbuckley/cabot-search huggingface dataset:
Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy
Authors: Catherine Alix-Panabières, Klaus Pantel
Journal: Cancer Discovery (2016)

Abstract “Liquid biopsy” focusing on the analysis of circulating tumor cells (CTC) and circulating cell-free tumor DNA (ctDNA) in the blood of patients with cancer has received enormous attention because of its obvious clinical implications for personalized medicine. Analyses of CTCs and ctDNA have paved new diagnostic avenues and are, to date, the cornerstones of liquid biopsy diagnostics. The present review focuses on key areas of clinical applications of CTCs and ctDNA, including detection of cancer, prediction of prognosis in patients with curable disease, monitoring systemic therapies, and stratification of patients based on the detection of therapeutic targets or resistance mechanisms. Significance: The application of CTCs and ctDNA for the early detection of cancer is of high public interest, but it faces serious challenges regarding specificity and sensitivity of the current assays. Prediction of prognosis in patients with curable disease can already be achieved in several tumor entities, particularly in breast cancer. Monitoring the success or failure of systemic therapies (i.e., chemotherapy, hormonal therapy, or other targeted therapies) by sequential measurements of CTCs or ctDNA is also feasible. Interventional studies on treatment stratification based on the analysis of CTCs and ctDNA are needed to implement liquid biopsy into personalized medicine. Cancer Discov; 6(5); 479–91. ©2016 AACR.
Assessment of regorafenib activity with FDG-PET/CT in a multicenter phase II study in patients (pts) with advanced gastrointestinal stromal tumor (GIST) following failure of standard therapy (Rx).
Authors: A. D. Van Den Abbeele, Y. Tanaka, T. Locascio, C. Sakellis, M. C. Heinrich, M. von Mehren, E. Choy, W. D. Tap, J. Manola, G. D. Demetri, S. George, J. T. Yap
Journal: Journal of Clinical Oncology (2011)

10050 Background: FDG-PET/CT is a pharmacodynamic biomarker with imatinib (IM) and sunitinib (SU) in GIST and correlates with clinical activity. This study evaluated FDG-PET/CT in a phase II trial of pts following failure of IM and SU who received regorafenib, a novel oral kinase inhibitor. Methods: Pts received regorafenib 160 mg/day orally d1-21 of each planned 28d cycle. Anatomic response was assessed with RECIST 1.1 pre-Rx and then after every 2 cycles of Rx. FDG-PET/CT was performed at baseline, then repeated at the end of Cycle 1 dosing (C1D21), end of the Cycle 1 washout planned week off Rx (C1D28), end of Cycle 2 dosing (C2D21), end of Cycle 4 dosing (C4D21), and at progression. SUVmax was assessed on up to 5 lesions per pt. The overall metabolic response was evaluated based on EORTC criteria by calculating the change in the sum of all lesions SUVmax at each follow-up time point relative to baseline. Correlations between early vs. late metabolic response, as well as concordance between metabolic response and RECIST 1.1, were evaluated with Kendall's W nonparametric statistical test. Results: As of Dec 2010, 26 pts were enrolled and had matched imaging with baseline and at least one follow-up FDG-PET/CT scan. At C1D21, 16 pts on regorafenib exhibited metabolic PR, 8 had SD, and 2 had PD. Of the 16 pts with metabolic PR, 10 showed a metabolic rebound during the time off regorafenib, with > 25% increase in the summed SUVmax at C1D28 relative to C1D21. There was strong agreement between metabolic response seen at C1D21 vs. C2D21 (W=0.93, p < 0.0001) and C4D21 (W=0.95, p < 0.0001). Most pts with metabolic PR had SD per RECIST 1.1. EORTC PET and RECIST 1.1 did not show a significant agreement at C2D21 (W=0.52, p=0.4481) or C4D21 (W=0.67, p=0.1340), with PET indicating metabolic response while RECIST showed stability in tumor size. Conclusions: Regorafenib induces significant early and sustained metabolic response in pts with advanced GIST following failure of IM and SU. Metabolic response precedes anatomic response by RECIST 1.1. Further analyses of early metabolic responses and long-term clinical outcomes are ongoing.
Phase I study of preoperative (pre-op) short course chemoradiation (CRT) with proton beam therapy (PBT) and capecitabine (cape) for resectable pancreatic ductal adenocarcinoma (PDAC) of the head
Authors: T. Hong, D. P. Ryan, L. S. Blaszkowsky, H. J. Mamon, M. Mino-Kenudson, J. Adams, B. Yeap, B. Winrich, T. F. DeLaney, C. Fernandez-del Castillo
Journal: Journal of Clinical Oncology (2009)

e15536 Background: Standard adjuvant 6 week CRT may delay and reduce tolerability of adjuvant gemcitabine-based chemotherapy. We explore the feasibility of a one-week course of pre-op CRT with PBT and cape followed by pancreaticoduodenectomy (PD). Methods: 15 pts with radiographically resectable, biopsy-proven PDAC of the head were enrolled from May 2007- September 2008. Eligibility included no CT involvement of SMA or celiac artery; adequate renal, hepatic and hematopoetic function; and ECOG PS 0/1. Dose level 1 consisted of PBT delivered 3 Gy x 10 Monday to Friday. Pts in subsequent dose levels received 5 Gy x 5 in progressively shortened schedules: level 2 (wk 1 M W F, wk 2 T Th), level 3 (wk 1 M T Th F, wk 2 M), level 4 (wk 1 M-F). Radiation was targeted at pancreatic mass with elective nodal coverage. Pts received Cape 825 mg/m2 BID wk 1 and 2 M-F. PD was performed 1–6 wks after completion of chemotherapy. Results: 15 pts were enrolled on study. 3 pts were treated at each of dose levels 1–3. 6 pts were at dose level 4, which was selected as MTD. No dose limiting toxicities were observed. Gr 3 toxicity was noted in 4 pts (pain-1, GI-1, stent obstruction/infxn- 2). 11 pts underwent resection. Reasons for no resections were: metastatic disease-3 and unresectable tumor- 1. Mean time from last therapy to surgery was 28 d (10–44). Mean post-PD length of stay was 6 days (range 5–10). No unexpected 30-d post-op complications, including leak or infection, were noted in comparison to historical controls. 9/11 resected pts had R0 resection. 9/11 had positive nodes. Mean resected tumor diameter was 2.9 cm (2.2–4.3). Average percentage of fibrosis in tumor mass was 74%. Conclusions: Pre-op CRT with 1 wk of PBT and capecitabine followed by early surgery is feasible. A phase II study is underway. No significant financial relationships to disclose.
Red Cross and Red Crescent draw up action plan
Authors: Tessa Richards
Journal: BMJ (1999)

The Red Cross and Red Crescent societies have made a commitment to a detailed action plan for 2000-3 to improve the care and protection of victims of armed conflict and of the world's most vulnerable people.

At their 27th international conference last month the two societies set key areas for action, including better protection of victims of conflict through greater respect of international humanitarian law and measures to improve the effectiveness of disaster relief. The plan underlines the need to be much better prepared for disasters and …
Phase II trial of irinotecan plus s-1 (IRIS) with cetuximab (IRIS/Cet) as second-line treatment in patients with <i>KRAS</i> wild-type metastatic colorectal cancer (mCRC): HGCSG0902—Comparison of administration interval in cetuximab treatment.
Authors: Yoshito Komatsu, Satoshi Yuki, Hiroshi Nakatsumi, Ayumu Hosokawa, Michio Nakamura, Osamu Muto, Takashi Meguro, Ichiro Iwanaga, Kazuteru Hatanaka, Yasushi Tsuji, Atsushi Sato, Kazunori Eto, Kouichi Furukawa, Manabu Onodera, Miki Tateyama, Yasuo Takahashi, Masayoshi Dazai, Sachio Yokoyama, Takuya Honda, Yuh Sakata
Journal: Journal of Clinical Oncology (2015)

746 Background: HGCSG0902 is the multicenter phase II study to investigate the safety and efficacy of IRIS/Cet as second-line treatment in patients with KRAS wild type mCRC. RR was 33.3% (95% CI, 20.8%-45.9%), therefore primary endpoint was met (Muto et al. ESMO 2014 ). Here we report an exploratory analysis of outcomes based on administration interval of Cet (every week [EW] vs bi-weekly [BW]). Methods: Eligibility includes histologically confirmed colorectal cancer, previously received oxaliplatin-contained chemotherapy, PS: 0-1, EGFR positive and KRAS WT. Pts. received S-1 80-120 mg/day p.o. on days 1-14 and irinotecan 100 mg/m 2 on days 1 and 15 repeated every 28 days. Cet was administrated 400 mg/m 2 as loading dose and continued 250 mg/m 2 every week or 500 mg/m 2 bi-weekly. The primary endpoint was RR and the secondary endpoints were disease control rate, PFS, OS and safety. To compare with EW and BW, Fisher’s exact test was used in terms of patient characteristics, AE, RR, and Log-rank test was used in terms of PFS, OS, and TTF. Results: Between March 2010 and September 2013, 58 pts were enrolled. One patient was not administered (57 pts were safety analysis set), and 3 pts were ineligible (54 pts were efficacy analysis set). Based on each physician choice, 34 pts. of EW and 23 of BW were included in the full safety analysis set. RR was 34.4% in the EW group and 31.8% in the BW group (p=1.000). Median PFS was 4.2 months (95% CI 3.5−4.9) in the EW group and 6.1 months (4.1-8.1) in the BW group (HR 0.752, 95% CI 0.413−1.372, p=0.350). The most common non-hematological adverse events of grade 3 or higher were diarrhea (23.5% in the EW group vs. 52.2% in the BW group: p=0.005) and stomatitis (2.9% in the EW group vs. 30.4% in the BW group: p=0.046), these were significantly more common in the BW group. Conclusions: IRIS/Cet appeared to be highly effective with RR and PFS in the both treatment schedule, and also had met the primary endpoint. Diarrhea and stomatitis were significantly more common in the BW group. Therefore, in case of treatment with IRIS, cetuximab should be administered weekly. Clinical trial information: 000004882.
Stress Chaperone Mortalin Contributes to Epithelial-to-Mesenchymal Transition and Cancer Metastasis
Authors: Youjin Na, Sunil C. Kaul, Jihoon Ryu, Jung-Sun Lee, Hyo Min Ahn, Zeenia Kaul, Rajkumar S. Kalra, Ling Li, Nashi Widodo, Chae-Ok Yun, Renu Wadhwa
Journal: Cancer Research (2016)

Mortalin/mthsp70 (HSPA9) is a stress chaperone enriched in many cancers that has been implicated in carcinogenesis by promoting cell proliferation and survival. In the present study, we examined the clinical relevance of mortalin upregulation in carcinogenesis. Consistent with high mortalin expression in various human tumors and cell lines, we found that mortalin overexpression increased the migration and invasiveness of breast cancer cells. Expression analyses revealed that proteins involved in focal adhesion, PI3K-Akt and JAK-STAT signaling, all known to play key roles in cell migration and epithelial-to-mesenchymal transition (EMT), were upregulated in mortalin-expressing cancer cells. We further determined that expression levels of the mesenchymal markers vimentin (VIM), fibronectin (FN1), β-catenin (CTNNB1), CK14 (KRT14) and hnRNP-K were also increased upon mortalin overexpression, whereas the epithelial markers E-cadherin (CDH1), CK8 (KRT8), and CK18 (KRT18) were downregulated. Furthermore, shRNA-mediated and pharmacological inhibition of mortalin suppressed the migration and invasive capacity of cancer cells and was associated with a diminished EMT gene signature. Taken together, these findings support a role for mortalin in the induction of EMT, prompting further investigation of its therapeutic value in metastatic disease models.
Abstract P183: Parents Play Significant Role in the Gender Differences Associated with Physical Activity in Elementary Students
Authors: Chelsea R Blankenship, Christa Ice, Vanessa Shannon, Lesley Cottrell
Journal: Circulation (2012)

BACKGROUND It has been proven that males engage in physical activity more than females starting at a young age. The goal of this study was to investigate gender differences based on parenting behaviors such as the frequency with which parents send their children out to play. METHODS Parents of children participating in a free cardiovascular risk-screening program (CARDIAC Project) completed a behavioral survey. Children (n =472; 43.3% female) who were enrolled in elementary school participated in the study. Parents provided information about children’s physical activity and their own ways in which they provided support of activity at home. Children’s participation in 12 activities was captured by total number of minutes per week. A combined mean activity score was calculated by summing the children’s total time across all of the activities. Parent behavior , specifically the frequency at which parents send their children outside to play was captured using a Likert scale where “1” represented never and “5” represented daily. Child gender and the amount of time allowed outside for play were then entered into a linear regression model to examine their role as potential predictors of child activity. RESULTS A significant gender difference (p&lt;.001) was noted in children’s total activity time with boys (n = 237; 751 minutes/week) exhibiting higher mean activity each week than girls (n = 229; 521 minutes/week). Child gender and the amount of time allowed outside to play significantly predicted children’s activity levels overall. This model explained 28.9% of the variance in children’s activity levels (F = 20.25 (2); p&lt;.001). Specifically, girls had less opportunity (3.75) than boys (4.05) to play outside. CONCLUSION A factor behind the lesser physical activity in female adolescents is significantly related to the decreased opportunity to play outside. Additional parenting practices will be shared if presented. In conclusion, parent behavior plays a significant role in the proven gender differences with childhood physical activity.
WHO strengthens Zika travel advice to pregnant women
Authors: Anne Gulland
Journal: BMJ (2016)

The World Health Organization has strengthened its advice to pregnant women, urging them not to travel to areas where the Zika virus is circulating.

The advice, issued after the second meeting of WHO’s emergency committee convened under the International Health Regulations, was issued in the light of stronger evidence of an association between the virus and fetal malformations. Previously, WHO had said that pregnant women should take precautions against mosquito bites if travelling to areas affected by Zika.1

Margaret Chan, WHO director general, told a press conference after the meeting on 8 March that the virus had been detected in amniotic fluid and had been shown to cross the placental barrier and infect …
Oral Cancer and Mouthwash Use&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: E L Wynder, G Kabat, S Rosenberg, M Levenstein
Journal: JNCI Journal of the National Cancer Institute (1983)

Journal Article Oral Cancer and Mouthwash Use Get access Ernst L. Wynder, M.D., Ernst L. Wynder, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Geoffrey Kabat, Ph.D., Geoffrey Kabat, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Saul Rosenberg, Ph.D., Saul Rosenberg, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Marcia Levenstein, Sc.D. Marcia Levenstein, Sc.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 70, Issue 2, February 1983, Pages 255–260, https://doi.org/10.1093/jnci/70.2.255 Published: 01 February 1983 Article history Received: 03 July 1982 Accepted: 21 September 1982 Published: 01 February 1983
Impact Of Treatment On Regulatory CD4+ T Lymphocytes, TH17 and Cytokines In Patients With Classical Hodgkin’s Lymphoma
Authors: Adriana M. Damasco Penna, Priscilla Brito Silva, Joyce M. K. Silva, Maria Mirtes Sales, Elma Maria Chaves, Joao Garibaldi Rezende, Egyla M Cavalcante, Otavio C. G. Baiocchi
Journal: Blood (2013)
Serum 1-OH vitamin D (D) and prognosis of postmenopausal breast cancer (BC) patients: NCIC-CTG MA14 trial
Authors: E. Piura, J. W. Chapman, A. Lipton, L. Zhu, K. Leitzel, C. F. Wilson, K. I. Pritchard, L. Shepherd, M. N. Pollak
Journal: Journal of Clinical Oncology (2009)

534 Background: In vitro, D has demonstrated regulatory functions in breast cancer cells and the bone microenvironment. Higher serum D levels were associated in some prior studies with favorable BC prognosis. We previously found that the baseline serum bone resorption marker, beta C-terminal telopeptides of type I collagen (B-CTx), was associated with bone-only first relapse, and that higher levels of insulin secretion as estimated by c-peptide level was associated with reduced event-free survival (EFS). We hypothesized that baseline serum D might be associated with relapse of breast cancer in bone and/or other metastatic sites. Methods: Baseline D was determined for the phase III MA.14 trial of adjuvant tamoxifen (20 mg/day oral for 5 years) ± octreotide (90 mg/month depot injection for 2 years). Stratification was by adjuvant chemotherapy, axillary lymph node status, and hormone receptor status. EFS, time from randomization to recurrence, second malignancy, or death due to any cause, was the primary endpoint. Recurrence-free survival (RFS), time from randomization to recurrence of the primary disease alone, was a secondary endpoint. For both endpoints, step-wise forward multivariate Cox regression adjusted for stratification factors was used to examine the association of D and outcome; a factor was added if p &lt; 0.05. Results: Baseline D levels were available for 607 (91%) patients. As expected, D levels for a population far from the equator varied with month of blood draw (p = 0.007), which gives confidence in assay performance. Continuous D was not associated with RFS of any relapse (p = 0.57), bone only relapse (p = 0.19), bone + other site of relapse (p = 0.73), or all bone relapse types (p = 0.66). D was not associated with EFS (0.43), even when adjusted by season (p = 0.64), level deficiency/insufficiency vs sufficiency/toxicity (p = 0.69), age (p = 0.54), and BMI (p = 0.32). As well, interactions between D and season, age, and BMI were non-significant (respectively, p = 0.90, 0.84, 0.23). Conclusions: D was not associated with EFS or RFS in postmenopausal breast cancer patients in this well controlled hormonal therapy study, a result consistent with some, but not all, studies of this issue. No significant financial relationships to disclose.
Prevalence of major depressive disorder in asthmatic patients
Authors: A Cappai, F Pinna, F Manunza, S Floris, E Zaccheddu, C Carruba Toscano, A Mancosu, S Palmieri, W Orru, L Gambula, F Argiolas, B Carpiniello, P Manconi, S Del Giacco
Journal: Allergy (2012)
Utilization and Outcomes Associated with Mobile-Based Asthma Action Plans Compared to Paper Asthma Action Plans Among Adolescents
Authors: Tamara T. Perry, Mallikarjuna R. Rettiganti, Jiang Bian, Chunqiao Luo, Dennis E. Schellhase, Shemeka M. Randle, Rita H. Brown, Ariel Berlinski, Sarah A. Marshall
Journal: Journal of Allergy and Clinical Immunology (2016)
Abstract 5559: Role of AMP-activated Protein Kinase in Ischemia-Reperfusion-Induced Barrier Failure in Endothelial Monolayers
Authors: Muhammad Assad, Muhammad Arshad, Frauke V Haertel, Muhammad Aslam, Ingrid Fleming, H M Piper, Thomas Noll
Journal: Circulation (2008)

Background: Ischemia-reperfusion provokes endothelial barrier dysfunction leading to edema formation and organ failure. The AMP-activated protein kinase (AMPK) is a fuel sensor which becomes activated under ischemia. It is now apparent that AMPK may also play important roles in stabilization of cell-adhesion. Here, it is hypothesized that AMPK may play an important role in protection barrier function under metabolic stress. Methods and Results: Overexpression of a dominant negative AMPK mutant in endothelial monolayers from human umbilical veins (EC) caused a 2-fold increase in basal permeability (albumin flux across the monolayers). In accordance, downregulation of AMPK by siRNA (~60%) leads to gap formation between adjacent EC, disintegration of cell adhesion structures and alterations of the cytoskeleton (loss of VE-cadherin at cell borders, actin stress fiber formation; immunocytochemistry), indicating that AMPK plays an important role in maintenance of barrier integrity. To analyse the role of AMPK on barrier function EC were exposed to ischemia (40 min, Po 2 &lt;5 mm Hg; pH 6.4) followed by reperfusion (40 min, Po 2 =140 mm Hg; pH 7.4). Ischemia caused an immediate increase in permeability (gap formation, video-imaging technique) and a 3-fold increase in AMPK activity (AMPK phosphorylation; western blot) after 40 min. During reperfusion gap formation was further increased by 307± 9 % (P&lt;0.05, n=5) within the ongoing 40 min. In contrast, AMPK phosphorylation rapidly declined to basal level within the first 10 minutes of reperfusion. However, addition of AICAR (AMPK activator; 5-aminoimidizole-4-carboxamide riboside), at the onset of reperfusion caused a rapid increase in AMPK phosphorylation and abolished the reperfusion-induced gap formation. Pretreatment of the cells with AICAR before the onset of ischemia reduced reperfusion-induced gap formation by 50 %. Conclusion: AMPK is involved in maintenance of cell-cell contacts and stabilization of basal barrier function. Pharmacological activation of AMPK within the first minutes of reperfusion can prevent hyperpermeability induced by reperfusion stress. Hence, activation of AMPK may provide a new therapeutic option to prevent ischemia-reperfusion barrier failure.
PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-Mediated Survival of Proneural Glioma Cells
Authors: Gilbert J. Rahme, Zhonghua Zhang, Alison L. Young, Chao Cheng, Eric J. Bivona, Steven N. Fiering, Yasuyuki Hitoshi, Mark A. Israel
Journal: Cancer Research (2016)

Abstract Glioblastoma is the most aggressive primary brain tumor and responds poorly to currently available therapies. Transcriptomic characterization of glioblastoma has identified distinct molecular subtypes of glioblastoma. Gain-of-function alterations leading to enhanced platelet-derived growth factor (PDGF) signaling are commonly observed in the proneural subtype of glioblastoma and can drive gliomagenesis. However, little is known about the downstream effectors of PDGF signaling in glioblastoma. Using a mouse model of proneural glioma and comparative transcriptomics, we determined that PDGF signaling upregulated ubiquitin-specific peptidase 1 (Usp1) to promote the survival of murine proneural glioma cells. Mechanistically, we found that PDGF signaling regulated the expression of the E2F transcription factors, which directly bound to and activated Usp1. Furthermore, PDGF-mediated expression of USP1 led to the stabilization of Inhibitor of DNA-binding 2 (ID2), which we found to be required for glioma cell survival. Genetic ablation of Id2 delayed tumor-induced mortality, and pharmacologic inhibition of USP1, resulting in decreased ID2 levels, also delayed tumorigenesis in mice. Notably, decreased USP1 expression was associated with prolonged survival in patients with proneural glioblastoma, but not with other subtypes of glioblastoma. Collectively, our findings describe a signaling cascade downstream of PDGF that sustains proneural glioblastoma cells and suggest that inhibition of the PDGF–E2F–USP1–ID2 axis could serve as a therapeutic strategy for proneural glioblastoma featuring increased PDGF signaling. Cancer Res; 76(10); 2964–76. ©2016 AACR.