tbuckley/cabot-search huggingface dataset:
Molecular profiling of response to platinum based therapy in non-small cell lung cancer (NSCLC) patients
Authors: R. D. Petty, G. I. Murray, K. Kerr, M. C. Nicolson, D. Bissett, E. Collie-Duguid
Journal: Journal of Clinical Oncology (2004)

2104 Background: Improved understanding of the molecular mechanisms underlying NSCLC pathogenesis and how these can be exploited by systemic therapies will lead to improved clinical outcomes. Using global gene expression profiling, we have previously shown that caspase independent programmed cell death pathways may be critical in mediating response to platinum based therapy in NSCLC. Methods: Tumour: uninvolved adjacent paired tissues from NSCLC patients who received platinum based neoadjuvant chemotherapy have been profiled (Affymetrix HG-U133A GeneChips). Gene expression data was validated using quantitative RT-PCR and data was analysed using Affymetrix MASv5.0, MicroDBv3.0, DMTv3.0 and GeneSpringv6. Results: In a supervised data analysis, inhibition of caspase dependent cell death is a universal finding in NSCLC which bears no correlation to response to therapy. In contrast, pathways of caspase independent cell death are blocked in non-responders but appear functional in responders. In non-responding tumours, many factors that stabilise the mitochondrial membrane are over-expressed in the tumour compared to the adjacent uninvolved tissue. In responding tumours a contrasting pattern is seen, with down-regulation of molecules that stabilise the mitochondrial membrane and up-regulation of molecules that increase mitochondrial membrane permeability (MMP). Conclusions:Our previous findings suggest that the functionality of caspase independent cell death pathways may be a critical factor in determining response to platinum based therapy in NSCLC. The data presented here supports this and suggests that increased MMP is a key event that may act as a trigger for an apoptotic-like caspase independent cell death process in response to platinum based chemotherapy. These pathways may provide important targets for novel therapeutics that have not previously been extensively investigated and may represent an approach that could be broadly applicable in the optimisation of treatment for other solid tumours. No significant financial relationships to disclose.
Abstract 19374: Predictors of Cardiovascular Events in Patients after Coarctation Repair
Authors: Paul Luijendijk, Ling Lu, Joris Vriend, Hubert Vliegen, Maarten Groenink, Maarten Groenink, Berto Bouma, Barbara Mulder
Journal: Circulation (2012)

Background: Long-term outcome after coarctation repair (CoA) is characterized by a significant cardiovascular morbidity and mortality Little is known on the predictive value of clinical parameters on cardiovascular events in CoA. The aim of this study is to determine the predictive value of clinical parameters on cardiovascular events. Methods: 160 adult CoA patients were identified in 2001 and followed for the occurrence of cardiovascular events until 2012. Echocardiography, ambulatory blood pressure monitoring, CMR imaging, and imaging of the carotid arteries (CIMT) were performed at baseline. The composite endpoint included: myocardial infarction, ischemic or hemorraghic cerebrovascular events, heart failure, aortic aneurysm formation requiring an intervention, and sudden cardiac death. Results: 160 adult CoA patients were included (mean age of 31.7 ±11.5 years and mean age at repair 4.3 ±6.6 years, 64% male) and followed with a mean follow-up of 10.10 ± 0.71 years; 18 (11%) patients suffered from an event during follow-up. Five patients (3%) had myocardial infarction, 4 (3%) an ischemic cerebrovascular accident, 7 (4%) an aortic aneurysm which needed surgical intervention, and 2 patients (1%) died suddenly. Univariate Cox regression analysis revealed that older age (ß = 1.08, P &lt; 0.001), elevated total cholesterol levels (β = 4.4; p = 0.03), elevated LDL cholesterol levels (β = 3.1, P = 0.09) and the carotid intima media thickness (β = 309.6; p = 0.007) were associated with an event during follow-up. Multivariate analysis demonstrated that patients with older age (β = 9.8, P = 0.02), increased total cholesterol levels (β = 1.24, P = 0.09) and an increased CIMT (β = 12.5, P = &lt; 0.001) were specifically at risk for a cardiovascular event during follow-up. Cumulative event-free survival was significantly lower in patients with a CIMT above 0.61 mm (median) (P = 0.09, HR: 2.23) (Figure 1) Conclusions: During 10 year follow up almost 11% of CoA patients suffered from a cardiovascular event. Older age, elevated cholesterol levels and an increased CIMT were the main determinants. Overall event-free survival is significantly lower in patients with an increased CIMT. Intervention with statin therapy might improve the prognosis of these young patients in the future.
Efficacy and tolerability of adjuvant modified FOLFOX-4 following chemoradioterapy for stage III rectum adenocarcinoma.
Authors: S. Cihan, D. Uncu, N. A. Babacan, H. Odabas, N. Ozdemir, O. B. Oksuzoglu, N. Zengin
Journal: Journal of Clinical Oncology (2010)

e14586 Background: The aim of this study is to investigate efficacy and toxicity of adjuvant chemoradiotherapy with a modified 5-fluorouracil (5-FU), folinic acid, oxaliplatin (mFOLFOX-4) regimen followed by infusional 5-FU concomitant with radiotherapy in patients with curatively resected stage III rectum adenocarcinoma. Methods: Patients with operated stage III rectum carcinoma were evaluated retrospectively. mFOLFOX-4 regimen (oxaliplatin 85 mg/m2 first day, folinic acid 200 mg/m2 first day, 5- FU 400 mg/m2 iv bolus first day, 5-FU 1,600 mg/m2 46 hours continuous infusion, every 2 weeks) had been given. After 4 courses of mFOLFOX-4, 50.4 Gy (1.8 Gy in 28 fractions) radiotherapy with continuous 5-FU 200 mg/m2/day by infusion pump during radiotherapy were given. After the end of chemoradiation, 4 more mFOLFOX-4 courses were given 15 days after chemoradiotherapy. Results: Between April 2005 and April 2008, 38 patients, of median age 51 years (range 23-69 years) were included in the study. Low anterior resection was done in 26 (68.4%) patients and abdominoperineal resection in 12 (31.6%) patients. Five (13.2%) patients were at stage IIIA, 16 (42.1%) patients were at stage IIIB and 17 (44.7%) patients were at stage IIIC. Planned chemotherapy cycles were completed in 92.1% of patients. Grade 3-4 toxicities included neutropenia (7.9%), febrile neutropenia (2.6%), anemia (2.6%), diarrhea (26.3%), renal toxicity (5.3%), hepatotoxicity (2.6%). Median follow-up time was 24 (8-42) months. Local recurrence and distant metastasis was observed in 3 (7.9%) and 7 (18.4%) patients, respectively. Two-year disease free and overall survival were 78% and 80%, respectively. Conclusions: mFOLFOX-4 following chemoradiotherapy with continuous 5- FU infusion is an effective and well tolerated adjuvant treatment for operated stage III rectal cancer. No significant financial relationships to disclose.
Abstract 90: Histopathological Lesions in the Hippocampal CA1 Region After 6 and 8 Minutes of Cardiac Arrest in Rats
Authors: Ursula Teubenbacher, Wolfgang Weihs, Florian Ettl, Ingrid Anna Maria Magnet, Petra Kodajova, Daniel Grassmann, Michael Wagner, Andreas Schober, Alexandra-Maria Warenits, Christoph Testori, Andreas Janata, Fritz Sterz, Sandra Högler
Journal: Circulation (2014)

Introduction:  Neuropathological damage in selectively vulnerable brain regions is an important outcome parameter in rodent models of ventricular fibrillation cardiac arrest (CA).   Hypothesis:  Different durations of cardiac arrest influence the extent of neuronal loss and glial reaction in the cornu ammonis (CA1) region of the hippocampus.   Materials and Methods:  CA was induced in male Sprague-Dawley rats, for 6 (n=7) or 8 min (n=6), 4 shams were included. Chest compressions, ventilation, drugs, and defibrillation were performed until return of spontaneous circulation (ROSC) was achieved. At day 14 animals were sacrificed. Brains were perfusion-fixed, embedded in paraffin and cut into 5 μm thick sections for histological evaluation. Viable neurons were counted in a 500 μm sector of CA1 in Nissl-stained sections. Immunohistochemistry was used to assess astrocyte and microglial activation semi-quantitatively with antibodies against GFAP and Iba1, respectively.   Results:  In Nissl-staining the sham group had 79±4 viable neurons. The 8 min group showed significantly less viable neurons (37±10; p   Conclusion:  Both CA durations produced consistent histological damage with loss of viable neurons, but the 8 min group showed more homogeneous results. Unexpectedly, the duration of CA was of no consequence for the level of glial activation. That suggests a similar glial reaction after neuronal loss regardless of its extent.
Abstract 16687: Abnormal Peripheral Muscle Oxygenation During Submaximal Exercise Contributes to Exercise Intolerance in Pulmonary Arterial Hypertension
Authors: Simon Malenfant, François Potus, Vincent Mainguy, Anne-Sophie Neyron, Evelyn Leblanc, Mathieu Malenfant, ève Tremblay, Sandra Breuils-Bonnet, François Maltais, Didier Saey, Sébastien Bonnet, Steeve Provencher
Journal: Circulation (2014)

Introduction: Pulmonary arterial hypertension (PAH) is a vascular remodeling disease leading to right ventricular failure. Despite the most modern therapies, most patients display persistent and significant exercise intolerance. Many observations suggest that exercise limitation in PAH is not simply due to pulmonary hemodynamic impairment, but that other determinants intrinsic to the skeletal muscle are involved. Hypothesis: We hypothesized that O2 delivery to skeletal muscles during exercise is impaired in PAH independently of cardiac output. Methods and Results: Ten PAH patients performed a submaximal exercise at 70% of their peak workload (mean workload = 58 (15) W). Ten healthy controls performed the same exercise at the same workload as the PAH patients with whom they were paired. The increase in muscle deoxyhemoglobin concentration [HHb] (near-infrared spectroscopy, ISS) of the dominant quadriceps was significantly higher in PAH patients compared to healthy controls (29.6 (3.7) vs 9.7 (2.5) %; p&lt;0.01) at the end of the submaximal exercise. This was not related to differences in cardiac output increases during exercise (+4.0 (0.7) vs +3.2 (0.4) L/min; p=0.29) (Nexfin BMEYE) or hemoglobin level (138.4 (2.4) vs 138.1 (3.7) g/L; p=0.94) for PAH patients and controls, respectively. Conversely, exercise-induced arterial O2 desaturation was more pronounced for PAH patients (-5.5 (1.8) vs -0.2 (0.6) %; p=0.03). Adding O2 supplementation did not significantly modified end-exercise muscle [HHb] (p=0.53), cardiac output increases (p=0.72) and arterial O2 desaturation (p=0.18). Quadriceps muscle biopsy confirmed that PAH patients had lower capillarity density compared to healthy controls (202 (27) vs 304 (23) #cap/mm2; p=0.01) that correlated with end-exercise muscle [HHb] (R2=0.37; p&lt;0.01). Finally, muscle [HHb] during submaximal exercise correlated with VO2 max (R2=0.65; p&lt;0.01) and 6 minutes walk test distance (R2=0.54; p=0.01). Conclusions: Our results demonstrate that PAH patients exhibit a lower skeletal muscle capillarity density that contributes to inadequate muscle O2 supply during exercise and exercise intolerance.
Circulating chromogranin A as a marker for poor-prognosis hormone refractory prostate cancer without neuroendocrine features: Prospective analyses of a cohort of patients
Authors: P. Maroto-Rey, N. Sala, J. Mora, H. Villavicencio, S. Esquena, L. Robert, J. Perez, J. Mazarico, A. Barnadas
Journal: Journal of Clinical Oncology (2009)

e16130 Background: Some patients may develop hormone refractory prostate (HRPC) cancer with neuroendocrine features, although they were not recognizable in the initial biopsy. Serum chromogranin is a marker for tumors with neuroendrocrine differentiation. Purpose: To analyze if serum levels of chromogranin A may identify poor prognosis HRPC patients in patients without neuroendocrine features in the initial biopsy. Methods: Circulating chromogranin A was prospectively analyzed in 34 patients when they were diagnosed under the standard criteria of HRPC. A patient was considered to have higher than normal levels of serum chromogranin if levels were above 100 ug/L. Patients were also assessed for serum PSA, enolase, serum alkaline phosphatase, albumin, and hemoglobin. Results were correlated with clinical prognostic factors as ECOG, PSA double time and Gleason score. We analyzed the time to hormone-refractory disease since diagnosis, and overall survival, as well as pattern of relapse (visceral vs. nonvisceral disease). Results: Median age was 63 (49–85). Median PSA was 33 (0.04–1455). At baseline, 16 patients were chromogranin-negative (46%), and 18 patients were chromogranin-positive (54). Chromogranin A did not correlate with either enolase or PSA. Patients with positive (&gt;100 ug/L) had stadistically significant lower levels of hemoglobine (13.8 vs 12.3), and a trend to have more visceral disease vs locoregional diasease or bone metastases, a lower albumine level (39.85 vs 45.05), higher alkaline phosphatase (221 vs 111), and LDH (1,914.5 vs 415). In this group of patients, we did not find differences in PSA double time, time to hormone-refractory disease or Gleason score. Conclusions: The analysis of this cohort of patients suggests that serum chromogranine A correlates with other known adverse prognosis factors of survival in prostate cancer patients. No significant financial relationships to disclose.
atpif1 regulates Mitochondrial Heme Synthesis In Developing Erythroid Cells
Authors: Dhvanit I Shah, Naoko Takahasi-Makise, Iman Schultz, Eric L Pierce, Liangtao Li, Guillaume Vogin, Benjamin S Brigham, Yi Zhou, Carlo Brugnara, Michelangelo Campanella, Nika Danial, Diane M Ward, Jerry Kaplan, Barry H Paw
Journal: Blood (2010)
RNAi-nanoparticulate manipulation of gene expression as a new functional genomics tool in the liver
Authors: Hao Yin, Roman L. Bogorad, Carmen Barnes, Stephen Walsh, Iris Zhuang, Hidenori Nonaka, Vera Ruda, Satya Kuchimanchi, Lubomir Nechev, Akin Akinc, Wen Xue, Marino Zerial, Robert Langer, Daniel G. Anderson, Victor Koteliansky
Journal: Journal of Hepatology (2015)
Accurate Needle Placement - A Must For a Safe and Effective Bone Marrow Biopsy Procedure: An Anatomical and CT Based Cadaver Study
Authors: Swati Pathak, Bhavana Konda, Inga Edwin, Priti L. Mishall, Sherry A. Downie, Todd R. Olson, Louis J. Reed, Ellen W. Friedman
Journal: Blood (2013)
Chronology of the arterial hypertension associated with inhibiting treatments of vascular endothelium growth factor receptor in patients with cancer.
Authors: J. Fuentes Pradera, J. Salvador Bofill, A. Grilo Reina, A. Lopez Ladron, R. Bernabe Caro, E. Fernandez Parra, I. Gallego, M. Rodriguez de la Borbolla
Journal: Journal of Clinical Oncology (2010)

e19638 Background: Angiogenesis plays a major role in the growth, invasion and metastasis of cancer. Drugs blocking the VEGF-receptor (bevacizumab and sunitinib) constitute a fundamental treatment in cancer. Hypertension (HBP) is a side effect of this class of drugs, frequently and potentially severe. HBP associated with these treatments presents in an oscillating and irregular way and is generally controlled by scarcely reliable means. Methods: We started a prospective study with the execution of pre- and post-treatment 24 h-ambulatory blood pressure monitoring (ABPM) and self-measured of BP every 12 hours at home, in patients with cancer under treatment with either bevacizumab or sunitinib with a view to identifying the variations in ABPM and the onset of HBP at an early stage so as to optimize treatment. For ABPM, a validated recording device (Spacelab 90207; Space Labs Medical; Redmond, WA) was used; a recording was made prior to the start of the anti-angiogenic treatment and 20 days (at least) after the first dose. An OMRON M6 tensiometer validated by the European HBP Society was used, with the ambulatory BP figures being collected at home as per standards. The primary goal is to find differences of at least 16 mmHg in the mean BP between the two ABPM readings. The first 8 patients are presented here. Results: N=8. Six patients received bevacizumab and two sunitinib. Mean age 50.1 years (26-71). One patient was known to be hypertensive. There is a mean interval of 31 days between the two ABPM readings. Differences of 5 and 4.6 mmHg were found between the mean systolic and diastolic BPs before and after treatment. For daytime systolic and diastolic BPs, the differences in the means were 3 and 2.5 mmHg while for nocturnal values they were 8 and 6 mmHg. A total of 1,040 pressure determinations were effected at home with a mean early-morning BP of 124.45/82.13 mmHg and 119.94/79.22 mmHg in the evening. There were 14 determinations with figures > 160/100. Conclusions: Treatment with anti-angiogenics in patients with cancer increases BP early on as measured by ABPM. The data point to a greater increase in nocturnal BP suggesting a non-dipper pattern. No significant financial relationships to disclose.
Implementing Quality Improvement for Psychosocial Interventions—Reply
Authors: Harold Alan Pincus, Mary Jane England
Journal: JAMA (2016)

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Long-term Follow-up after lodine-131 Treatment for Plummer??s Disease (Autonomous Goiter)
Authors: JAN D. WEINER
Journal: Clinical Nuclear Medicine (1985)

A follow-up study is presented in 88 patients treated with I-131 for Plummer's disease (localized autonomous thyroid function, either multifocal or as a solitary nodule) one to 17 years before the present study. Studies included clinical examination, scintigraphy, and function tests. One patient was hypothyroid, seven were marginally hyperthyroid, and five still received low dose antithyroid drugs. Of 75 euthyroid patients, the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) was absent in 16 (generally with scintigraphic evidence of autonomous function), subnormal in 20, and normal in 39. A single autonomous nodule prior to treatment was found relatively frequently in males and in patients with a normal TRH test at follow-up. Most goiters had become smaller and one third of all solitary nodules could not be detected anymore. Autonomous function at follow-up was probably due to residual rather than recurrent disease in most, if not all, cases. It is concluded that I-131 therapy is at least as satisfactory as partial thyroidectomy in the treatment of Plummer's disease; lifelong follow-up was not found to be necessary.
Growth of Carcinomas in the Region of the Cartilage
Authors: W. Dontenwill, H.-J. Chevalier, G. Reckzeh
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Growth of Carcinomas in the Region of the Cartilage Get access W. Dontenwill, W. Dontenwill Research Institute of the Cigarette Industry, Hamburg, Gazellenkamp, 38, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar H.-J. Chevalier, H.-J. Chevalier Research Institute of the Cigarette Industry, Hamburg, Gazellenkamp, 38, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Reckzeh G. Reckzeh Research Institute of the Cigarette Industry, Hamburg, Gazellenkamp, 38, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 1, January 1973, Pages 291–293, https://doi.org/10.1093/jnci/50.1.291 Published: 01 January 1973 Article history Received: 10 November 1972 Accepted: 01 December 1972 Published: 01 January 1973
Single-agent capecitabine as maintenance therapy after induction of XELOX (or FOLFOX) in first-line treatment of metastatic colorectal cancer: randomized clinical trial of efficacy and safety
Authors: H.Y. Luo, Y.H. Li, W. Wang, Z.Q. Wang, X. Yuan, D. Ma, F.H. Wang, D.S. Zhang, D.R. Lin, Y.C. Lin, J. Jia, X.H. Hu, J.W. Peng, R.H. Xu
Journal: Annals of Oncology (2016)
Urine Metabolite Profiles Predictive of Human Kidney Allograft Status
Authors: Karsten Suhre, Joseph E. Schwartz, Vijay K. Sharma, Qiuying Chen, John R. Lee, Thangamani Muthukumar, Darshana M. Dadhania, Ruchuang Ding, David N. Ikle, Nancy D. Bridges, Nikki M. Williams, Gabi Kastenmüller, Edward D. Karoly, Robert P. Mohney, Michael Abecassis, John Friedewald, Stuart J. Knechtle, Yolanda T. Becker, Benjamin Samstein, Abraham Shaked, Steven S. Gross, Manikkam Suthanthiran
Journal: Journal of the American Society of Nephrology (2015)

Noninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may help realize the full benefits of kidney transplantation. To investigate whether urine metabolites predict kidney allograft status, we determined levels of 749 metabolites in 1516 urine samples from 241 kidney graft recipients enrolled in the prospective multicenter Clinical Trials in Organ Transplantation-04 study. A metabolite signature of the ratio of 3-sialyllactose to xanthosine in biopsy specimen-matched urine supernatants best discriminated acute cellular rejection biopsy specimens from specimens without rejection. For clinical application, we developed a high-throughput mass spectrometry-based assay that enabled absolute and rapid quantification of the 3-sialyllactose-to-xanthosine ratio in urine samples. A composite signature of ratios of 3-sialyllactose to xanthosine and quinolinate to X-16397 and our previously reported urinary cell mRNA signature of 18S ribosomal RNA, CD3ε mRNA, and interferon-inducible protein-10 mRNA outperformed the metabolite signatures and the mRNA signature. The area under the receiver operating characteristics curve for the composite metabolite–mRNA signature was 0.93, and the signature was diagnostic of acute cellular rejection with a specificity of 84% and a sensitivity of 90%. The composite signature, developed using solely biopsy specimen-matched urine samples, predicted future acute cellular rejection when applied to pristine samples taken days to weeks before biopsy. We conclude that metabolite profiling of urine offers a noninvasive means of diagnosing and prognosticating acute cellular rejection in the human kidney allograft, and that the combined metabolite and mRNA signature is diagnostic and prognostic of acute cellular rejection with very high accuracy.