tbuckley/cabot-search huggingface dataset:
Phase Ii Study of First-Line Mfolfox Plus Cetuximab (C) for 8 Cycles Followed By Mfolfox Plus C or Single Agent (S/A) C As Maintenance Therapy in Patients (P) with Metastatic Colorectal Cancer (Mcrc): the Macro-2 Trial (Spanish Cooperative Group for the Treatment of Digestive Tumors [Ttd])
Authors: P. García Alfonso, M. Benavides, A. Sánchez Ruiz, C. Guillen-Ponce, M.J. Safont, J. Alcaide, A. Gómez, R. Lopez, J.L. Manzano, M. Mendez Urena, F. Rivera, J. Sastre, C. Grávalos, T. García García, J.I. Martin-Valades, E. Falco, E. González Flores, M. Navalón, E. Diaz Rubio, E. Aranda
Journal: Annals of Oncology (2014)
Circulating endothelial cells and progenitor cells in metastatic renal cell cancer: Predictive value during anti-angiogenic therapy?
Authors: F. Farace, P. Vielh, A. Plantade, S. Amsellem, L. Bouaita, G. Vassal, J. M. Bidart, K. Fizazi, B. Escudier
Journal: Journal of Clinical Oncology (2007)

3555 Background: Anti-angiogenic therapy has demonstrated efficacy in the treatment of metastatic renal cell carcinoma (MRCC). New surrogate biomarkers are needed to optimize the potential of this novel therapy. Circulating endothelial cell (CEC) and progenitor cell (CEP) measurement has been proposed to monitor anti-angiogenic drug activity and treatment efficiency. Methods: 21 patients (pts) with MRCC were analysed. Among them, 16 were monitored both at baseline and 2 -3 weeks after start of anti-angiogenic treatment (14 pts received sutinimib and 2, nexavar). CECs were measured in one ml erythocyte lysed whole blood by four color flow cytometry (FCM) and identified by a CD45 - CD31 + CD146 + 7-amino-actinomycin (7AAD) - phenotype. Enumeration of CEC was validated by spiking whole blood with human umbilical vein cells and by immunohistochemical staining of the cell sorted fraction with endothelial markers (Ulex-Europaeus-lectin-1 and Von Willebrand factor). Median CEC value in 20 healthy subjects was 5.5 /ml (range 0–15) wheras this value was 16/ml (range 0–179) in 80 metastatic cancer patients. CEPs were measured by FCM as extremely rare events with a CD45 dim CD34 + VEGFR2 + 7AAD - phenotype. Results: Median MRCC baseline CEC value was 17/ml (range 3 to 101). 16 pts had CEC levels that were two-fold greater than healthy subjects (&gt;10/ml). Preliminary data showed a dramatic drop in CEC levels in patients that responded to therapy. Median baseline CEP value was 0.49% of hematopoietic stem cells (HSC), with ranges from 0.06% to 9% (absolute counts: 10/ml range 1 to 181/ml). Eight patients had CEP values greater than 1% of HSC and all had high tumor burden. Among the 16 pts monitored, all except 2 showed a dramatic increase in CEPs after treatment suggesting that anti-VEGFR2 targeted therapy might induce peripheral accumulation of CEP. Updated data and correlations with prognostic factors and clinical outcome will be presented. Conclusion: During anti-angiogenic therapy, dramatic changes in both CEC and CEP levels were observed. Predictive values of CEC and CEP are currently under evaluation. No significant financial relationships to disclose.
Letter by Bulluck and Hausenloy Regarding Article, “Air Versus Oxygen in ST-Segment–Elevation Myocardial Infarction”
Authors: Heerajnarain Bulluck, Derek J Hausenloy
Journal: Circulation (2016)

The use of high-flow oxygen in the setting of acute myocardial infarction remains controversial.We therefore read with great interest the randomized, controlled clinical trial by Stub et al, 1 which investigated the effect of supplementary oxygen versus air in normoxic patients presenting with an acute ST-segment-elevation myocardial infarction.In their study, the authors concluded that supplementary oxygen therapy may increase early myocardial injury and is associated with larger myocardial infarct size assessed by cardiovascular magnetic resonance at 6 months in patients who have ST-segment-elevation myocardial infarction.However, the data provided in the study do not appear to support this conclusion.First, it was based on a difference in peak levels of serum creatine kinase between the 2 groups.However, creatine kinase is known to be less specific for myocardial necrosis, 2 and the study had not been originally powered to detect this end point.The authors had actually powered the study based on peak levels of serum troponin I, a more specific biomarker for myocardial necrosis than creatine kinase, and for which there was no significant difference between the 2 groups.Second, they reported a difference in myocardial infarct size at 6 months in grams measured by cardiovascular magnetic resonance, but when this was normalized to left ventricular mass, there was no significant difference between the 2 groups.In the absence of T2-weighted cardiovascular magnetic resonance imaging to quantify the area-at-risk, the authors could have used coronary angiographic jeopardy scores to estimate the area-at-risk and calculate myocardial salvage, 3,4 an approach that has previously been used to validate T2-weighted cardiovascular magnetic resonance imaging.In summary, the data do not appear to support the conclusion that supplemental oxygen may be harmful in normoxic patients who have ST-segment-elevation myocardial infarction in comparison with air-rather, it shows no added benefit with this therapeutic approach.
Zinc Finger Nucleases Targeting The β-Globin Locus Drive Efficient Correction Of The Sickle Mutation In CD34+ Cells
Authors: Megan D Hoban, Alok V Joglekar, David Gray, Michael L Kaufman, Fabrizia Urbinati, Shantha Senadheera, Gregory Cost, Andreas Reik, Michael C. Holmes, Philip D Gregory, Roger P. Hollis, Donald B. Kohn
Journal: Blood (2013)
Tumors in CF-1 Mice Exposed for Six Consecutive Generations to DDT
Authors: V. S. Turusov, N. E. Day, L. Tomatis, E. Gati, R. T. Charles
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Tumors in CF-1 Mice Exposed for Six Consecutive Generations to DDT Get access V. S. Turusov, V. S. Turusov Search for other works by this author on: Oxford Academic PubMed Google Scholar N. E. Day, N. E. Day Search for other works by this author on: Oxford Academic PubMed Google Scholar L. Tomatis, L. Tomatis Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Gati, E. Gati Search for other works by this author on: Oxford Academic PubMed Google Scholar R. T. Charles R. T. Charles Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 3, September 1973, Pages 983–997, https://doi.org/10.1093/jnci/51.3.983 Published: 01 September 1973 Article history Received: 19 March 1973 Accepted: 09 May 1973 Published: 01 September 1973
Reproducibility of diagnosis in patients with myelodysplastic syndrome
Authors: J. A. Burger, G. Borthakur, S. Pierce, H. Kantarjian, E. Estey
Journal: Journal of Clinical Oncology (2006)

16506 Background: The myelodysplastic syndromes (MDS) have been considered notoriously difficult with regard to reliability of diagnosis and proper classification. The diagnosis and subclassification of MDS is based on hematopathology studies on the peripheral blood and marrow, along with cytogenetic and clinical information. Determination of single or multiple lineage dysplasia, percentage of myeloblasts, grading of cellularity, fibrosis, and iron content are essential for establishing the diagnosis of MDS. Methods: We reviewed the diagnosis of 112 patients who were referred to MD Anderson Cancer Center (MDACC) with an outside diagnosis of MDS. Results: Between July and December 2005, 112 patients were referred to MDACC with a diagnosis of MDS (bone marrow blast percentage &lt;30%). Upon review of bone marrow studies performed at MDACC, diagnosis of MDS was confirmed in 83 patients. Acute myelogenous leukemia (AML) was diagnosed in 11 patients, and 3 patients were diagnosed to have myeloproliferative disorder (MPD) or chronic myelomonocytic leukemia (CMML). Alternate diagnosis offered in 18 patients included other cause of anemia (6), normal marrow (3), large granular lymphocyte leukemia (2), uncertain (2), immune thrombocytopenia (1), and multiple myeloma (1). Excluding 14 patients with AML or MPD/CMML (since they may represent natural progression of disease), diagnosis other than MDS was established in 15% (18/98) of patients. Conclusions: Upon review, diagnosis other than MDS is made in a significant percentage of patients referred with a diagnosis of MDS. As such, repeat blood and marrow workup and evaluation by more than one hematopathologist increases the accuracy of diagnosis in MDS and should be mandatory for clinical trials in MDS. No significant financial relationships to disclose.
Impact of the Comprehensive Health Enhancement Support System (CHESS), an interactive computer support system (ICSS) on non small cell lung cancer (NSCLC) survival: A randomized study comparing CHESS with the internet
Authors: J. F. Cleary, L. L. Dubenske, M. K. Buss, C. L. Carmack Taylor, A. Atwood, A. M. Traynor, R. Govindan, A. Bhattacharya, F. McTavish, D. H. Gustafson
Journal: Journal of Clinical Oncology (2008)

8088 Background: Advanced NSCLC patients continue to have high mortality with median survivals less that one year despite advances in anti-cancer therapies. This high mortality and symptom burden impacts quality of life (QOL) of both patients and their caregivers. CHESS, an ICSS, has previously improved the QOL of early breast cancer patients through the provision of support, information, and skill building to its users. The current CHESS lung cancer module also included a Clinician Report that provided patient and caregiver self report of symptom burden and areas of distress. Our primary hypothesis was that CHESS, provided to NSCLC patients and their caregivers, will improve caregiver QOL and bereavement. Methods: Metastatic NSCLC patients (and their caregivers), recruited throughout the course of their illness at 4 major cancer centers, were randomized to receive internet or CHESS. All dyads were provided with computers and internet access for home use if not already available. Symptom burden and QOL measures, along with web usage were collected at regular intervals, from both patients and caregivers. Patient survival was calculated as the date from the time of randomization. Results: 234 patients were randomized, with equivalent staging and performance status in the two groups. 36, 42 and 156 patients were Stage IIIA, IIIB and IV respectively. Exploratory logrank testing examining the 6–12 month post-intervention segment of the survival curve demonstrated a significant survival advantage for CHESS over the Internet (Χ2=5.343, p=.021). One year survival was significantly increased in the CHESS group (50%) compared to the internet (34.2%) (t= -2.096, p=0.038). Conclusion: This result, while unexpected, shows a survival benefit for advanced NSCLC patients given access to CHESS, and is viewed with some caution given that it falls outside the primary hypothesis. The results and its mechanism will be studied in a replicative study with the primary endpoint of survival. The survival advantage could be due to reduced symptom burden leading to increased performance status and QOL, resulting in increased benefit from anti-cancer therapies. No significant financial relationships to disclose.
Autologous hematopoietic cell transplantation (HCT) for non-Hodgkin lymphoma (NHL) in patients over 60 years of age
Authors: A. Karampeazis, E. Ayala, W. Poling, L. Balducci, C. Anasetti
Journal: Journal of Clinical Oncology (2008)

20620 Background: High dose chemotherapy followed by autologous HCT is the treatment of choice for relapsed NHL. Safety and efficacy in elderly patients has not been adequately studied. Methods: This is an IRB approved review of records. Patients with NHL, older than 60 years, treated with HCT between August 1998 and August 2007 were included. Correlation was made between pre-existing comorbidity and toxicity or early death. Results: Sixty-two patients with a median age of 65 years were evaluated. Thirty-eight had diffuse large B-cell lymphoma, 7 had follicular, 7 mantle cell, 8 peripheral T-cell, while 2 had other subtypes. At transplant, 15 patients had primary refractory disease, 19 were on first or second CR, 26 were on first or second relapse and the status of 2 pts was unknown. Fifty-three patients had chemosensitive disease, 6 had chemoresistant disease and 2 had unknown status. Median number of prior regimens is 2. Median Cumulative Illness Rate Scale-Geriatric (CIRS-G) score was 3.5 while median adjusted Charlson and Sorror scores were 0.67 and 1.33, respectively. Twenty-three pts received conditioning with cyclophosphamide, busulfan and etoposide, 15 received carmustine, etoposide, cytarabine, and melphalan (BEAM), 12 BEAM plus rituximab and 12 other regimens. Median CD34+ cells infused was 5.31x106 cells/Kg. Median days to neutrophil and platelets engraftment was 11 and 14 days respectively. With a median follow-up of 9.2 months, overall survival is 50.5% at 2 years and 37.8% at 4 years. Event-free survival is 45.3% at 2-years and 31% at 4 years. There were 3 early treatment- related deaths (4.8%), due to VOD, sepsis syndrome and c.difficile colitis. Neutropenic fever and culture-positive infection ocurred in 53 and 19 patients, respectively. Twenty-five patients developed grade 3–4 mucositis or enteritis, 3 had grade 3 renal toxicity, 1 grade 3 pulmonary, 1 grade 3 hepatic and 3 multi-organ toxicity. Median time of hospitalization was 20 days. There was no significant correlation between comorbidity and transplant related mortality, grade3–4 toxicity or days of hospitalization. Conclusions: Autologous HCT is safe for selected NHL patients over 60 years of age with low comorbidities, and the efficacy is comparable to that in younger patients. No significant financial relationships to disclose.
Updated results of a phase II trial of therapy with cyclophosphamide (CYP)/pentostatin/rituximab for indolent NHL and CLL
Authors: M. Odaimi, R. Farah, T. Terjanian, M. Vesoniaraki, P. Friscia, A. Rubin, M. Dhar, Q. Dai, F. Forte, J. Burton
Journal: Journal of Clinical Oncology (2005)

6713 Background: Indolent NHL and CLL are initially chemosensitive, but are incurable by conventional chemotherapy. Pts often receive multiple courses of chemotherapy; thus, effective treatment with low cumulative toxicity (particularly myelotoxicity) is desirable. Pentostatin alone or in combination has shown activity in NHL and CLL, with a favorable toxicity profile. Thus, we evaluated this chemo/rituximab regimen in indolent NHL and CLL pts who were previously untreated or treated with up to 3 prior regimens (sensitivity to the prior regimen is required). Methods: 28 pts have been enrolled thus far, of whom 24 are evaluable for tumor response and 25 for toxicity. The treatment plan for the first 10 pts included 4 cycles of therapy q 3-weeks, including 2 doses of rituximab and 1 dose of CYP+pentostatin per cycle; after an amendment, the last 18 pts received 6 Rx cycles (1 dose of rituximab in cycles 5 & 6). Pneumocystis prophylaxis was provided. In pts evaluable for response, there are 7 CLL and 17 NHL pts. 10 pts had received prior therapy. Results: Objective responses were confirmed in 20/24 (83%) pts (6 CRs; 14 PRs; 2 unconfirmed PR; 2 SD). Best confirmed tumor responses are shown in the table below. Response durations have ranged from 5–36+ months. One dose reduction of CYP was permitted, which was needed in only 5 pts. G-CSF was used in only 11 treatment cycles in 5 pts. 9 pts had reversible grade 3 or 4 neutropenia. Also, serial CD4+ and CD34+ counts were obtained in the last 10 pts to further assess hematologic toxicity (results to be presented). Non-hematologic toxicity was mild. There were 2 suspected cases of pneumonia, and 1 case of H. zoster post-therapy. One pt died of an intracranial bleed 2 months post-Rx and one pt had grade 3–4 fatigue requiring discontinuation after 4 cycles. Conclusion: This regimen is well tolerated, effective and, despite initial concerns, opportunistic infections were not a problem. Supported in part by SuperGen, Inc. No significant financial relationships to disclose.
Performance of a blood-based gene-expression test, BCtect, for early breast cancer detection
Authors: D. Tobin, K. Bårdsen, M. Kauczynska, Y. Kumar, C. Shroff, D. Punia, V. Srinivasan, A. Børresen Dale, P. Sharma, A. Hollingsworth
Journal: Journal of Clinical Oncology (2009)

11012 Background: We report the development of a gene expression based blood test to detect breast cancer (BC). Validation of the test has been performed in multiethnic populations (European/US and Indian). Here we report findings from a multi-centre validation study. Methods: In a multicentre-study, blood samples were collected from women recruited in 4 groups 1) early stage BC, 2) late stage BC, 3) benign breast lesions, 4) without abnormal mammographic findings. Samples were collected in PAXgene tubes and shipped to a central laboratory where RNA extraction and quality control were performed. Gene expression analysis was performed using TaqMan low density arrays containing a BC-specific gene signature in a 96-gene assay format. The overall gene expression pattern was converted to a test score which was used to classify the subject as positive or negative for BC. A total of 442 samples were used to develop an India specific algorithm and estimate its prediction efficacy. Samples were divided into a training cohort (N=292) and a test cohort (N=150). The performance of the test was determined from the class of the independent test cohort. Results: The model correctly predicted the class of 110/150 test samples, resulting in an overall accuracy of 73%. Performance was similar for early and late stage cancer and for benign and healthy (no mammographic findings). No significant difference in diagnostic performance was seen between pre- (57/75 correctly predicted) and post-menopausal (53/75 correctly predicted) women indicating the clinical value of our test in younger women. No statistical correlation between correct/false test score and body mass index was noted. Lesion size varied from 8mm diameter to 120mm. No statistical correlation of the test score was seen with lesion size in this cohort. Conclusions: The blood based gene expression test showed similar diagnostic performance between women with early and late stage BC, and the test was independent of the subject's BMI and menopausal status suggesting broad applicability of the test and indicating its clinical potential in younger women where mammography is of less value due to dense breast tissue. No correlation with lesion size was seen suggesting the lower limit of detection is below 8mm. [Table: see text]
Influence of high values of air pollutants on number of asthma exacerbations in children from Pancevo in years 2009 and 2010
Authors: Stanisa Baumann, Slobodan Prodanovic, Stefan Baumann, Jasmina Prodanovic, Svetlana Pakaski, Marija Deanovic, Milica Tanaskovic
Journal: European Respiratory Journal (2011)

Introduction:  Air pollution is well known for it9s influence on development of asthma. Children with asthma are specially vulnerable on high levels of air pollutants.   Aim:  To show that elevated air pollution (tar, SO 2 , NO 2, TSP, NH 3  and benzene) have significant influence on acute exacebations of asthma in children.   Method and results:  We have monitored daily concentrations of tar, SO 2 . NO 2,  TSP, NH 3  and benzene in city of Pancevo in October, November, December, January and February and number of children who visited pediatrician due to acute asthma exacerbation. We have excluded other months to avoid influence of higher levels of pollen. We have observed that during periods with high peaks of tar, TSP and benzene, larger number of children had acute asthma exacerbation and visited pediatrician. SO 2,  NO 2  and NH 3  were within legally permited range.  Results have shown that in year 2009 in January, February, October, November and December tar, TSP and benzene were above permited values 73 days and in that period 1736 children had asthma exacerbation. In the same period in 2010 the same air pollutants were 44 days above permited values and 939 children had asthma exacerbation. During periods with air polution below permited values in 2009, 1331 children had asthma exacerbation in 78 days, and in 2010, 1508 in 107 days. This difference is statistically significant, which was confirmed by χ 2  – test, for year 2009 χ 2  = 3.987, and for 2010 χ 2  was 4.91, p> 0.05.   Conclusion:  High concentrations of tar, TSP and Benzene have significant influence on larger number of asthma exacerbations in children, specialy during periods of oversteping legally permited concentrations.
P36 Block of interferon γ and co-culture with smDCs enhance antigen-specific T-reg suppression ability in autoimmune hepatitis type 2
Authors: M S Longhi, G Mieli-Vergani, Y Ma, D Vergani
Journal: Gut (2010)

Introduction  CD4posCD25high regulatory T-cells (T-regs), central to immune homeostasis, are impaired in autoimmune hepatitis type 2 (AIH-2), a severe disease often leading to end-stage liver damage despite immunosuppression. T-regs specific for cytochrome P450IID6 (CYP2D6), the target autoantigen in AIH-2, can be expanded in vitro and exert a stronger suppressor function over damaging effector T-cells than non antigen-specific T-regs.  Aim  To explore the mechanisms controlling antigen-specific T-reg suppressor function in AIH-2.  Method  13 AIH-2 patients positive for the HLA-DR7 and DR3 predisposing MHC alleles, were studied. Peptide-pulsed semi-mature dendritic cells (smDCs) were obtained from CD14pos cells following treatment with IL-4, GM-CSF, interferon-λ and CYP2D6 peptides. CYP2D6-T-regs were obtained after CD4posCD25high cell purification from CD14neg cells cultured for 8 days in presence of CYP2D6 peptide, high dose interleukin-2 (IL-2) and T-cell expander. Frequency of interferon (IFN)-γ, IL-2, IL-17, IL-4, IL-10 and TGF-β producing cells within CYP2D6-T-regs was tested before and after 2-day co-culture with smDCs (smDC-CYP2D6-T-regs) by intracellular staining; suppressor function was determined by proliferation assay after T-reg addition to CD25neg target cells.  Results  There was no difference in the frequency of IL-2, IL-17, IL-4, IL-10 and TGF-β producing CYP2D6-T-regs in the absence or presence of smDCs, while IFN-γ-producing cells were more frequent in the absence of smDCs (1.39±0.3 vs 0.4±0.1; p=0.046). Treatment with anti-IFN-γ neutralising antibody decreased the frequency of IFN-γ-producing cells within CYP2D6-T-regs to 0.46±0.2 (p=0.041) and enhanced their suppressor function over CD25neg cell proliferation from 23% to 45.6% (p=0.04), this value being similar to that obtained after adding smDC-CYP2D6-T-regs (50%). As engagement of the signalling molecule B7-H1 on smDCs inhibits IFN-γ secretion, we tested whether its blockage affects the number of IFN-γ-producing cells and/or smDC-CYP2D6-T-reg suppressor function. Interestingly, blockage of B7-H1 did not affect smDC-T-regs ability to suppress despite incrementing the frequency of IFN-γ-producing cells (1.63±0.08; p  Conclusion  In AIH-2 T-reg suppression ability is enhanced by control of IFN-γ production and by co-culture with peptide-pulsed smDCs. These manoeuvres should be considered to obtain highly potent clinical-grade T-regs for immunotherapy. The mechanism through which smDCs augment suppression remains to be clarified.
Margaret McCartney: Mindful of mindfulness
Authors: Margaret McCartney
Journal: BMJ (2016)

Are you paying attention to the present moment, in a non-judgmental way?Are you undistracted?Do you feel "here" and grounded?The modern mindfulness movement has gained wide support in Britain, far beyond its use in mental health services.But the National Institute for Health and Care Excellence approves the technique only for preventing and treating some mental illnesses.