tbuckley/cabot-search huggingface dataset:
Neoadjuvant chemotherapy including bevacizumab in potentially curable metastatic colorectal cancer
Authors: B. Gruenberger, W. Scheithauer, D. Tamandl, H. Puhalla, G. Kornek, C. Zielinski, T. Gruenberger
Journal: Journal of Clinical Oncology (2006)

3546 Background: the addition of targeting therapies to combination chemotherapy have dramatically improved outcome in metastatic colorectal cancer (mCRC). Special issues have been raised regarding the sequence of bevacizumab (bev) administration and surgery in mCRC. Methods: a pilot series of non-optimal resectable mCRC patients was initiated including a neoadjuvant protocol with bevacizumab 5mg/kg every two weeks plus XELOX (capecitabine 3500mg/m 2 /day days 1–7 plus oxaliplatin 85mg/m 2 day 1 of a 2-week cycle) for six cycles (3 months). The sixth cycle did not include bev resulting in a gap of 5 weeks between last bev and surgery. Additional 6 cycles were started 5 weeks after surgery. Primary end points were feasibility of the regimen, possibility of curative surgical approach and morbidity of the surgical procedure including liver resection. Results: we have enrolled 22 patients of whom 12 are evaluable for all primary endpoints today. Median age of the patients was 61.5 years (± 8.8), 83% had a lymph node positive primary, 67% had synchronous liver metastases (LM), 33% had bilobar LM. The neoadjuvant treatment regimen was safely administered resulting in 2 CR, 8 PR and 2 SD; XELOX was dose reduced to 75% due to HFS, diarrhoe or PNP ≥ 3 in 3 patients (25%). Potentially curative surgery was performed in all but one patient (92%) including liver resection in 11 patients, involving additional resection of the primary in 3 patients. No patient required perioperative blood transfusions, morbidity consisted of one bile leak from the resection edge and one wound infection. No patient experienced bleeding complications or showed postoperative liver dysfunction. Median postoperative hospital stay was 7 days (± 1.7). All patients started adjuvant treatment within 5 weeks. Liver regeneration as evaluated during staging CTs confirmed no abnormalities. Conclusions: these data suggest that bevacizumab can be administered prior and after potentially curative surgery including liver resection without appearing to adversely effect surgical wound healing, bleeding or liver regeneration. However we would like to emphasize that patients need to be treated by an experienced multidisciplinary team including a liver surgeon qualified in dealing with chemotherapy altered livers. [Table: see text]
The methylome of pediatric acute myeloid leukemia.
Authors: Stanley Pounds, Xueyuan Cao, Susana Raimondi, James Downing, Raul Correa Ribeiro, Jeffrey E. Rubnitz, Jatinder Kaur Lamba
Journal: Journal of Clinical Oncology (2015)

10027 Background: DNA methylation can alter gene expression by either creating binding sites for methylation-dependent repressor proteins, or by disrupting the binding of transcription factors to their target sequences. DNA methylation has been studied extensively and associated with survival in adults with AML. However, a detailed genome-wide study of epigenetic regulation of gene expression and its pharmacological and clinical impact in pediatric AML patients has not been performed. Methods: In this study, we obtained Illumina 450K methylation array profiles for 175 pediatric patients and Affymetrix U133A gene expression arrays for 166 pediatric patients treated in the multicenter AML02 clinical trial (NCT00136084). Results: We found a very significant canonical correlation of methylation with expression (FDR ≤ 0.01) in 1,978 genes with several of the top ranked genes having established roles in the biology and treatment of AML. An analysis adjusting for risk group found that the canonical correlation methylation and expression variables of 24 genes showed statistically significant evidence of a biologically meaningful pattern of associations with in vitro sensitivity to cytarabine, minimal residual disease assessed by flow cytometry after the first course of chemotherapy, and event-free survival (p ≤ 0.001; FDR ≤ 0.32). Finally, we observed differential methylation according to clinical risk group at 36,667 markers scattered throughout the genome (FDR ≤ 0.01) with low-risk patients showing hypomethylation at 32,920 of those 36,667 (89.8%) markers. Conclusions: Given the methylation differences in clinical risk groups incorporation of demethylating agents might be a useful strategy to improve the outcome of high-risk AMLs by modifying the methylome to more closely resemble that of low-risk AMLs, which are most sensitive to cytarabine. Our results illustrate the power of combined profiling of methylation and expression to improve our understanding of the disease and the molecular level and identify potentially useful therapeutic targets.
Routine use of sentinel lymph node surgery in patients undergoing prophylactic mastectomy: A decision analysis model
Authors: J. C. Boughey, J. N. Cormier, Y. Xing, F. Meric-Bernstam, M. I. Ross, G. V. Babiera, F. C. Ames, K. K. Hunt, I. Bedrosian
Journal: Journal of Clinical Oncology (2006)

607 Background: Patients with invasive carcinoma identified following prophylactic mastectomy (PM) require axillary lymph node dissection (ALND) for nodal staging as standard surgical treatment. Since most patients will be node negative, sentinel lymph node (SLN) surgery has been advocated to avoid the sequelae of unnecessary axillary surgery. However, since SLN surgery is not without complications and the incidence of invasive cancer in PM is extremely low, we sought to compare surgical strategies using a decision analysis model in order to define the true risks and benefits of routine SLN surgery versus standard surgical treatment (ALND). Methods: Model estimates were derived by systematic review of the literature. The outcomes examined were: (1) the number of SLN procedures that would need to be performed to avoid one ALND in a pathologically node negative patient; and (2) the probability of long-term axillary complications with each strategy. Occult breast cancer was defined as invasive cancer in the PM specimen and/or SLN metastases. Results: The following weighted averages were used to inform the model: i) incidence of invasive cancer in PM of 1%, ii) incidence of nodal disease of 25% in the presence of invasive breast cancer and 1% in the absence of invasive cancer in the breast, and iii) incidence of complications after ALND of 30% and after SLN surgery of 6%. Routine use of SLN surgery doubled the sensitivity for detection of carcinoma compared to ALND. However, 133 SLN procedures were required to avoid one ALND in a node negative PM patient. Additionally, the probability of complications per breast cancer detected was 10-fold greater with the SLN strategy. When the risk of breast cancer was projected at 10%, 13 SLN procedures were required to avoid one negative ALND and the complication rate per cancer detected was 2-fold greater in the SLN arm. Conclusions: The benefit of adding SLN surgery in patients undergoing PM depends on the probability of detecting invasive cancer. Routine SLN surgery in PM is not warranted given the large number of procedures required to benefit one patient and the complications associated with performing SLN surgery in all patients. However, the SLN strategy may be appropriate for subgroups of patients at higher risk of occult carcinoma. No significant financial relationships to disclose.
More viral mutants, less HBsAg clearance? One size may not fit all
Authors: Tai-Chung Tseng, Hung-Chih Yang, Jia-Horng Kao
Journal: Gut (2016)

Dear Sir,

We read with great interest the article by Bayliss et al 1 e-published in August 2016.

HBV is a DNA virus and viral mutants develop during the course of persistent infection because of the spontaneous error of viral reverse transcription. Some of the viral mutants will be selected and become the predominant strains under the pressure of host immunity if they bear better replication fitness. Two common HBV mutants, mutations in precore stop codon (PC) (G1896A) and basal core promoter (BCP) (A1762T/G1764A), have been shown to abolish or reduce the production of HBeAg, respectively, which contribute to disease progression.2 In previous reports, these viral variants were determined using population sequencing, which is a qualitative assay thus limits …
GW26-e2341 Prevalence of Congenital Heart Disease in Xinjiang Multi-Ethnic Region of China
Authors: Fen Liu, Yining Yang, Xiang Xie, Xiaomei Li, Xiang Ma, Zhenyan Fu, Bangdang Chen, Ying Huang, Chunfang Shan, Xiaoming Gao, Yitong Ma
Journal: Journal of the American College of Cardiology (2015)
<i>Notes from the Field:</i>Pediatric Emergency Department Visits for Buprenorphine/Naloxone Ingestion — United States, 2008–2015
Authors: Daniel S. Budnitz, Maribeth C. Lovegrove, Mathew R.P. Sapiano, Justin Mathew, Scott R. Kegler, Andrew I. Geller, Christian Hampp
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Expanding access to office-based medication-assisted treatment with buprenorphine/naloxone for opioid dependence is a key part of the national strategy to address the opioid abuse epidemic (1). However, as buprenorphine/naloxone prescribing increased, emergency department (ED) visits and hospitalizations for unsupervised ingestions by young children began to increase, with buprenorphine/naloxone ingestions becoming the most common cause of hospitalization for medication ingestions by young children during 2010-2011 (2). Buprenorphine ingestions might be asymptomatic or can cause drowsiness, vomiting, or respiratory depression, which if untreated can result in death (3). Buprenorphine/naloxone was available only as tablets in multidose child-resistant bottles (Suboxone) until late 2010, when film strips packaged in unit-dose, child-resistant pouches were introduced. In 2013, tablets became available in unit-dose packaging (Zubsolv). Because unit-dose, child-resistant packaging encloses each dose until opened, it might limit unintended ingestions by young children compared with traditional child-resistant bottles that must be resecured after every use (4). This study compared ED visits for pediatric buprenorphine/naloxone ingestions before and after these product packaging/formulation changes.
Colorectal Cancer Screening Recommendations
Authors: Phillip Levine, Milena Gould-Suarez
Journal: JAMA (2016)

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Clinical Implications of Reticulin Fibrosis of Bone Marrow in De Novo Acute Myeloid Leukemia.
Authors: Tzung-Chih Tang, Hung Chang, Chien-Feng Sun, Lee-Yung Shih, Po Dunn, Po-Nan Wang, Jin-Hou Wu, Ming-Chung Kuo, Tung-Liang Lin, Yu-Shih Hung, Hsiao-Wen Kao
Journal: Blood (2012)
P0581 : Prediction of HBsAg seroclearance and HBsAg seroconversion in a cohort of inactive european hepatitis B (HBV) carriers: A prospective longitudinal study (albatros study)
Authors: V. Knop, E. Herrmann, J. Vermehren, J. Petersen, P. Buggisch, H. Wedemeyer, M. Cornberg, S. Mauss, M. Sprinzl, T. Berg, F. van Bömmel, H. Klinker, D. Hüppe, M. Rausch, T. Welzel, A. Vermehren, S. Susser, S. Zeuzem, C. Sarrazin
Journal: Journal of Hepatology (2015)
LAG 3/MHC 2 and PD 1/PD L1 expression in non-small cell lung cancer patients.
Authors: Yayi He, Hui Yu, Rafal Dziadziuszko, Ellison Kim, Chris Rivard, Kowalewski Ashley, Rozeboom Leslie, Shengxiang Ren, Caicun Zhou, Fred R. Hirsch
Journal: Journal of Clinical Oncology (2016)

3039 Background: Immunotherapy targeting the PD1/PDL1 checkpoint has shown promising efficacy in patients with non-small cell lung cancer (NSCLC). LAG-3/MHC II is another important checkpoint that may have a synergistic interaction with PD-L1/PD-1. In this study, we describe the protein expression of LAG 3, MHC 2, PD 1 and PD L1 and their associations with survival in patients with NSCLC. Methods: The expression of LAG3 (EPR4392, Abcam), MHC II (DP, DQ, DR) (CR3/43, Abcam), PD 1 (NAT 105, Cell marque) and PD L1 (22C3, Dako) was evaluated in 139 surgically resected specimens from patients with NSCLC by immunohistochemistry (IHC). Results: LAG 3 was expressed on the immune cells in 49 (35.3%) patients. MHC II was expressed in 37 (26.6%) patient tumor cells. 60 samples (43.2%) stained positive for PD 1 on the immune cells, and 25 (18.0%) had positive PD L1 expression on tumor cells. There was no LAG 3 or PD 1 expression on tumor cells. LAG 3 on immune cells was overexpressed in squamous carcinoma compared to adenocarcinoma (P = 0.044). MHC II on tumor cells was expressed less in squamous carcinoma (P = 0.043) and smokers (P = 0.004) compared to adenocarcinoma and non-smokers. LAG 3 expression on immune cells was correlated with the expression of PD 1 (P＜0.001) on immune cells and PD L1 (P = 0.006) on tumor cells. Expression of PD L1 on tumor cells and PD 1 on immune cells were positively correlated (P = 0.026). Expression of PD L1 on tumor cells and on immune cells was negatively correlated (P = 0.819). PD L1 (tumor cells) negative patients had a longer disease free survival (DFS) (1.85 years [95% CI 0.41–3.28] vs. 0.97 years [0.709–1.231]; P = 0.038). DFS was longest in both PD L1 and LAG 3 negative patients（PD L1 on tumor cells and LAG 3 on immune cells）, followed by patients for only PD L1 or LAG 3 positive, and DFS was shortest in patients positive for both PD L1 and LAG 3 (2.09 years [95% CI 0.25-3.93] vs. 1.76 years [0.67-2.85] vs. 0.67 years [0.17-1.18]; P = 0.018). Cox regression analysis showed that positive LAG 3 expression on immune cells was a poor prognostic factor for NSCLC patients (P = 0.040, EXP (B) 1.964, 95%CI 1.030-3.747). Conclusions: LAG 3 expression was correlated with PD 1/PD L1 expression and was associated with poor prognosis in patients with NSCLC.
Once a Week Bortezomib with Dexamethasone Is Effective with Limited Toxicity in Newly Diagnosed Multiple Myeloma Patients with Older Age and Co-Morbidities,
Authors: Nikhil C. Munshi, Saem Lee, Suman Kambhampati, Michal Rose, Abid Mohiuddin, Yvonne Efebera, Andrew Han, Antoun Houranieh, Abraham Zimelman, Mary T. Brophy, Rao Prabhala, Terrence Grady, Paulette Mehta, Teresa G Hayes, Sarvari Venkata Yellapragada, Caroline Behler, Catherine Klein, David Roodman, Alan K. Lichtenstein
Journal: Blood (2011)
A phase I trial of gemcitabine (Gem), 17-allylaminogeldanamycin (17-AAG) and cisplatin (CDDP) in solid tumor patients
Authors: P. Haluska, D. O. Toft, S. M. Steinmetz, A. Furth, S. Mandrekar, B. A. Stensgard, A. K. McCollum, L. J. Hanson, A. A. Adjei, C. Erlichman
Journal: Journal of Clinical Oncology (2004)

3058 Background: 17-AAG, a benzoquinone ansamycin derivative that targets the heat shock protein hsp90, is currently undergoing clinical evaluation in phase I/II trials. We have demonstrated sequence dependent synergy with Gem and CDDP in combination with 17-AAG in vitro. Methods: A phase I trial was conducted in patients with solids tumors receiving the sequential administration of Gem → 17-AAG → CDDP. The goals were to establish the MTD, evaluate toxicity, clinical activity and effects on surrogate markers. Patients were given escalating doses of Gem (from 750–1000 mg/m2), and fixed doses of 17-AAG (154 mg/m2) and CDDP (40 mg/m2), on days 1 and 8, q21d. Peripheral blood mononuclear cells (PBMCs) were collected at 0, 6 and 25 hours after treatment for evaluation of surrogate markers. Results: To date, 12 patients (9F/3M; median age 51) have received 25 cycles of therapy. Tumor types included three ovarian, three lung and one each of thyroid, sarcoma, liver, appendix, breast and melanoma. Four DLTs, comprising gr3 ANC, gr3 elevated liver enzymes, dehydration, hyponatremia, nausea, vomiting and gr3 platelets, were observed at dose level 2 (Gem 1000 mg/m2, 17-AAG 154 mg/m2, CDDP 40 mg/m2). Non-dose limiting toxicities were anorexia (50%), constipation (33%), fatigue (42%), anemia (75%), leukopenia (67%), nausea (75%), neutropenia (42%), thrombocytopenia (42%), and vomiting (42%). Two PRs (ovarian cancer) and 2 SD (> 3 months for both) in NSCLC and breast cancer were seen out of 8 evaluable patients., There was a significant increase in hsp70 protein expression at 6 and 25 hours (p<0.03), and a decrease in the level of the hsp90 client protein, ILK at 6 hours (p=0.02), in PBMCs. Conclusions: The combination of Gem, 17-AAG, and CDDP demonstrated activity with significant toxicity, likely secondary to Gem and CDDP. Hsp70 and ILK are useful surrogate markers of 17-AAG effecting its target. Currently this study is being amended to administer 17-AAG in combination with either GEM or CDDP, alone. (Supported in part by CA15083, CA69912, CA90390, and M01-RR00585) Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Kosan Biosciences
ABC Transporter Expression in Acute Myeloid Leukemia: Association with in Vitro Cytotoxicity and Prognostic Markers
Authors: Ajay Abraham, Savitha Varatharajan, Sreeja Karathedath, Ashok kumar Jeyavelu, Shaji R Velayudhan, Rayaz Ahmed, Aby Abraham, Biju George, Mammen Chandy, Alok Srivastava, Vikram Mathews, Poonkuzhali Balasubramanian
Journal: Blood (2012)
Case-Control Studies Are Not Familial Studies
Authors: Zhe Wang, A. Dessa Sadovnick, Anthony L. Traboulsee, Jay P. Ross, Cecily Q. Bernales, Mary Encarnacion, Irene M. Yee, Madonna de Lemos, Talitha Greenwood, Joshua D. Lee, Galen Wright, Colin J. Ross, Si Zhang, Weihong Song, Carles Vilariño-Güell
Journal: Neuron (2016)
A Randomized Trial of Tbo-Filgrastim Versus Filgrastim for Autologous Stem Cell Mobilization in Patients with Multiple Myeloma or Non-Hodgkin Lymphoma
Authors: Mark A Fiala, David Schwab, Ravi Vij, Amanda F. Cashen, Keith Stockerl-Goldstein, Camille N. Abboud
Journal: Blood (2015)
Development and validation of a mathematical equation to estimate glomerular filtration rate in cirrhosis: The royal free hospital cirrhosis glomerular filtration rate
Authors: Maria Kalafateli, Fred Wickham, Maria Burniston, Evangelos Cholongitas, Eleni Theocharidou, Matteo Garcovich, James O'Beirne, Rachel Westbrook, Gioacchino Leandro, Andrew K. Burroughs, Emmanuel A. Tsochatzis
Journal: Hepatology (2016)

Current expressions based on serum creatinine concentration overestimate kidney function in cirrhosis, leading to significant differences between “true” and calculated glomerular filtration rate (GFR). We compared the performance of the four‐variable and six‐variable Modification of Diet in Renal Disease and chronic kidney disease epidemiology with “true,” or measured, GFR (mGFR) and the impact of this difference on Model for End‐Stage Liver Disease (MELD) calculation. We subsequently developed and validated a GFR equation specifically for cirrhosis and compared the performance of the new derived formula with existing GFR formulae. We included 469 consecutive patients who had a transplant assessment between 2011 and 2014. mGFR was measured using plasma isotope clearance according to a technique validated in patients with ascites. A corrected creatinine was derived from the mGFR after application of the Modification of Diet in Renal Disease formula. Subsequently, a corrected MELD was calculated and compared with the conventionally calculated MELD. Stepwise multiple linear regression was used to derive a GFR equation. This was compared with the mGFR in independent external and internal validation sets of 82 and 174 patients with cirrhosis, respectively. A difference &gt;20 mL/minute/1.73 m 2 between existing formulae and mGFR was observed in 226 (48.2%) patients. The corrected MELD score was ≥3 points higher in 177 (37.7%) patients. The predicted equation ( r 2 = 74.6%) was GFR = 45.9 × (creatinine –0·836 ) × (urea –0·229 ) × (international normalized ratio –0·113 ) × (age −0.129 [Corrected November 29, 2016: originally written as “age‐129.”]) × (sodium 0·972 ) × 0.809 (if female) × 0.92 (if moderate/severe ascites). An online calculator is available at http://rfh-cirrhosis-gfr.ucl.ac.uk. The model was a good fit and showed the greatest accuracy compared to that of existing formulae. Conclusion : We developed and validated a new accurate model for GFR assessment in cirrhosis, the Royal Free Hospital cirrhosis GFR, using readily available variables; this remains to be tested and incorporated in prognostic scores in patients with cirrhosis. (H epatology 2017;65:582‐591).
UK must act quickly to become world leader in regenerative medicine, MPs hear
Authors: Adrian O’Dowd
Journal: BMJ (2016)

The United Kingdom has to move quickly to become a world class base for regenerative medicine, a rapidly developing science that could lead to groundbreaking new ways of providing care for patients, MPs have been told.

The window of opportunity for the UK to be a global centre for this kind of research and medicine—which includes cell therapy, gene therapy, and tissue engineering—is narrow, experts told MPs on the House of Commons science and technology committee during an evidence session on 19 October for its inquiry into regenerative medicine.

Time constraints were highlighted by one witness, Ian McCubbin, an employee of GlaxoSmithKline and co-chair of the Advanced Therapy Manufacturing task force, which is set to publish an action plan next month to anchor advanced therapy commercial …