tbuckley/cabot-search huggingface dataset:
Lenalidomide, Bortezomib, and Dexamethasone (RVD) in Combination with Vorinostat As Front-Line Therapy for Patients with Multiple Myeloma (MM): Results of a Phase 1 Study
Authors: Jonathan L. Kaufman, Jatin J. Shah, Jacob P. Laubach, Alaina R. Mitchell, Cathy Sharp, Colleen Lewis, R. Donald Harvey, Charise Gleason, Daniela Casbourne, Ajay K. Nooka, Leonard T Heffner, Paul G. Richardson, Robert Z. Orlowski, Sagar Lonial
Journal: Blood (2012)
Rapid gene isolation in barley and wheat by mutant chromosome sequencing
Authors: Javier Sánchez-Martín, Burkhard Steuernagel, Sreya Ghosh, Gerhard Herren, Severine Hurni, Nikolai Adamski, Jan Vrána, Marie Kubaláková, Simon G. Krattinger, Thomas Wicker, Jaroslav Doležel, Beat Keller, Brande B. H. Wulff
Journal: Genome biology (2016)

Identification of causal mutations in barley and wheat is hampered by their large genomes and suppressed recombination. To overcome these obstacles, we have developed MutChromSeq, a complexity reduction approach based on flow sorting and sequencing of mutant chromosomes, to identify induced mutations by comparison to parental chromosomes. We apply MutChromSeq to six mutants each of the barley Eceriferum-q gene and the wheat Pm2 genes. This approach unambiguously identified single candidate genes that were verified by Sanger sequencing of additional mutants. MutChromSeq enables reference-free forward genetics in barley and wheat, thus opening up their pan-genomes to functional genomics.
Prognostic factors in metastatic colorectal carcinoma at initial diagnosis, MCCID
Authors: C. T. Vallejo, A. O. Zwenger, J. A. Lacava, J. Iturbe, J. E. Perez, M. Machiavelli, A. Romero, M. E. Dominguez, R. Rodriguez, B. Leone
Journal: Journal of Clinical Oncology (2007)

14548 Background: Despite several studies have evaluated the role of prognostic factors (PF) in metastatic colorectal cancer, results are controversial. The aim of the present study was to assess PF in a homogeneous population with MCCID treated with biochemical modulation of 5- Fluorouracil-based regimens. Methods: Analyses were based on individual data of 318 patients (P) with MCCID treated in different prospective trials at GOCS Institutions since May 1984 to Jun 2001. The following variables (V) were considered: a) Clinical variables (CV): age, sex, family history of CC, hypertension, diabetes, tabaquism, weight loss, and performance status (PS), b) Tumor variables (TV): histologic grade, size and location of primary tumor; number of metastatic sites, number and size of liver metastases, uni- bilateral liver involvement; and c) Laboratory variables (LV): CEA, lactate dehydrogenase (LDH), alkaline phosphatase, ALT, AST, and hemoglobin. Overall survival (OS) was analyzed since date of diagnosis by means of Kaplan-Meier and the Log-rank test was used to assess the differences. A Cox’s proportional hazard modeling was used for multivariate analyses. Results: The OS for the entire group was 18.1 months (IC95, 15.0–22.7). Univariate analysis showed statistical significance in the following; a) CV: family history CC (p=0.001), PS (p=0.04), diabetes (P=0.003); b) TV: histologic grade (p=0.01), uni-bilateral liver involvement (p&lt;0.0001), number of liver metastases (p&lt;0.0001) and size of liver metastases (p&lt;0.0001); and c) LV: hemoglobin (p=0.05), ALT (P=0.0006), AST (p&lt;0.0001), alkaline phosphatase (p&lt;0.0001), LDH (p=0.0004); Cox’s analyses showed statistical significance only for PS and alkaline phosphatase (p= 0.01 and p=0.0001, respectively). Conclusions: In this setting of P with MCCID the PS remains the most important PF for OS. High value of alkaline phosphatase may reflect liver involvement. No others PF considered in the analyses had prognostic influence. No significant financial relationships to disclose.
Long-term supportive treatment with fermented mistletoe (viscum album L.) extract in primary nonmetastatic colorectal cancer: Best time to start with for optimal effectiveness
Authors: H. Matthes, W. E. Friedel, P. R. Bock
Journal: Journal of Clinical Oncology (2009)

e15099 Background: Safety and efficacy of fermented mistletoe extract (Iscador, ISC) in supportive care of post-surgical patients with primary colorectal cancer as compared to a parallel control group without ISC. Question: Is supportive ISC most effective when started before, during, or after radio- and/or chemotherapy? Methods: In a comparative, multicenter, non-interventional cohort study with parallel groups ISC was applied additionally to conventional adjuvant chemo- and/or radiotherapy (conv-th). The control group was treated with conv-th only. Unselected, standardized, anonymized data from medical records (1993–2002) meeting the eligibility criteria were followed until last visit or death. The pre-specified endpoints were the incidence of adverse drug reactions (ADR) caused by conv-th, and disease-free survival (DFS) in relation to start of ISC therapy before, during or after conv-th. All endpoints were adjusted to confounders. Results: 804 eligible patients (429 ISC and 375 control) from 26 centers were evaluated. ISC started mostly during conv-th (72.9%), and sometimes before (9.0%) or after (18.1%) conv-th. ISC dose was escalated from 0.01mg to 20mg as s.c. injection, 2–3 times weekly. The median follow-up time was 58 (ISC) vs. 51 months and median ISC duration was 52 months. The adjusted relative ADR risk was significantly lower in the ISC groups as compared to control: odds ratio, OR (95% CI) = 0.46 (0.28–0.77), p=0.003. The best results were found in patients where ISC started in parallel to conv-th. Analysis of DFS in the ISC subgroups is presently ongoing. ISC was well tolerated in all subgroups. Conclusions: The results show reliable safety and clinically relevant beneficial effects of ISC treatment, at best if applied in parallel to conv-th. [Table: see text]
Primary Prophylaxis Prevents the Onset of Arthropathy: Longitudinal Results of 603 Boys with Severe Factor VIII Deficiency Analyzed through the Centers for Disease Control Universal Data Collection (CDC UDC) Study.
Authors: Marilyn J. Manco-Johnson, Chengbin Wang, Barbara A. Konkle, Robina Ingram-Rich, Steven Humes, J. Michael Soucie
Journal: Blood (2008)
Abstract IA10: Convergent control of cancer associated fibroblast activation and field cancerization by Notch/CSL and p53 signaling
Authors: G. Paolo Dotto, G. Paolo Dotto
Journal: Cancer Research (2016)

Abstract The vast majority of epithelial cancers is limited to in situ lesions that, for internal organs like breast, prostate or lung, can remain undetected for the whole life of an individual. The reason(s) why only a minor fraction of these lesions progresses into malignancy is not understood. Changes in tumor stroma are most frequently viewed as secondary to changes in the epithelium. However, recent evidence indicates that they may play a primary role. Such a possibility would help explain not only dormancy of most epithelial cancers, but also field cancerization, a condition of major clinical significance linked with multifocal and recurrent tumors and broader tissue changes beyond areas of tumor development that expand over time. Stromal fibroblast senescence has been linked to aging-associated cancer risk. However, density and proliferation of cancer associated fibroblasts (CAF) are frequently increased. In the mouse, deletion of the Notch effector CSL/RBP-Jκ in dermal fibroblasts is sufficient for CAF activation and ensuing multifocal keratinocyte tumors. We report that CSL silencing induces senescence of primary fibroblasts of both mouse and human origin, and from dermis, oral mucosa, breast and lung. CSL functions in these cells as direct repressor of multiple senescence- and CAF-effector genes. It also physically interacts with p53, repressing its activity. CSL is down-modulated in stromal fibroblasts of premalignant skin actinic keratosis lesions and squamous cell carcinomas (SCC), while p53 expression and function is down-modulated only in the latter, with paracrine FGF signaling as likely culprit. Concomitant loss of CSL and p53 overcomes fibroblast senescence, enhances expression of CAF effectors and promotes stromal and cancer cell expansion. The findings support a CAF activation/stromal co-evolution model under convergent CSL/p53 control. Citation Format: G. Paolo Dotto, G. Paolo Dotto. Convergent control of cancer associated fibroblast activation and field cancerization by Notch/CSL and p53 signaling. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr IA10.
Reforms to research and higher education risk “unprecedented” interference, UK scientist warns
Authors: Gareth Iacobucci
Journal: BMJ (2016)

The UK government’s radical shake up of research and higher education risks eroding institutional autonomy and academic freedom, a leading UK scientist has warned.

Stephen Curry, professor of structural biology at Imperial College London, warned that proposals set out in the Higher Education and Research Bill would expose universities to an “unprecedented level of interference” from politicians.

But other eminent UK scientists argued that the bill—which is currently being debated in parliament—would actually give UK science a greater influence on government and allow it to push for an increase on the “pitiful” amount of funding it currently received.

The bill sets out a series of changes designed to make it easier for new providers from the private sector to enter the higher education sector, to …
PD-0022 Aflibercept Versus Placebo in Combination with Folfiri in Previously Treated Metastatic Colorectal Cancer: Mean Overall Survival for Subgroups from Velour
Authors: Florence Joulain, Sheikh Iqbal, Françoise Diamand, Eric Van Cutsem, Martin Hoyle, Carmen Allegra
Journal: Annals of Oncology (2012)
Prior Therapy with Rituximab (R) in Patients (pts) with Diffuse Large B-Cell Lymphoma (DLBCL) Does Not Affect Disease-Free (DFS) or Overall Survival (OS) Following High Dose Therapy (HDT) and Autologous Stem Cell Transplantation (ASCT).
Authors: Snehal G. Thakkar, John William Sweetenham, Lisa Rybicki, Ronald Sobecks, Steven Andresen, Robert M. Dean, Brad Pohlman, Tyler Y. Kang, Matt Kalaycio, Stacey Brown, Brian J. Bolwell
Journal: Blood (2006)
A prospective survey evaluating the use of soy products in breast cancer
Authors: S. Walker, J. Franciose, P. G. Vashi, C. Lammersfeld, J. F. Grutsch, C. G. Lis, D. Gupta, S. Williams
Journal: Journal of Clinical Oncology (2006)

10562 Background: Many studies have evaluated the potential role of soy in the prevention of breast cancer. A number of components in soy appear to have anticancer properties, including isoflavones, genistein and daidzein. The use of soy by women with breast cancer is now being questioned because of the estrogen-like effects of isoflavones and possible interactions with tamoxifen. Clinicians providing nutrition counseling to these women are concerned because the availability of soy foods has increased dramatically in the past few years. The goal of this study was to quantify the intake of isoflavones in women with breast cancer to determine if their intake is of clinical significance. Methods: We evaluated a consecutive case series of 100 women with breast cancer treated at Cancer Treatment Centers of America between 09/03 and 02/04. After obtaining informed consent, each patient was asked to complete a soy food frequency questionnaire (FFQ) that was scored by Fred Hutchinson Cancer Research Center, the institute that developed and validated FFQ. Results: Mean age was 50.5 years (std. dev. = 9.4; range 31–70) and mean BMI was 27.3kg/m 2 (std. dev. = 6.75; range 17–59). Table 1 shows detailed characteristics of our patients. Genistein and Daidzein consumption was limited to 65 patients with a mean intake of 81.5 mg/week (std. dev. = 153; range 0.02–682) and 52.9 mg/week (std. dev. = 98.8; range 0.02–482) respectively. Soy foods with highest reported consumption were soy sauce (37%), soy milk (23%), soy bars (18%), roasted soy nuts (13%) and tofu (13%). Conclusions: Our study suggests that the isoflavone intake of breast cancer patients at our hospital was quite variable. Thirty-five patients reported no soy intake. The mean daily intake translates into 11.6 mg genistein and 7.4 mg daidzein, which is equivalent of less than ¼ cup of tofu per day. This amount is slightly higher than what has been previously reported in non-Asian American women. [Table: see text] No significant financial relationships to disclose.
Pomalidomide in myeloproliferative neoplasm-associated myelofibrosis
Authors: R F Schlenk, F Stegelmann, A Reiter, E Jost, N Gattermann, H Hebart, C Waller, A Hochhaus, U Platzbecker, P Schafhausen, I W Blau, W Verbeek, F H Heidel, M Werner, H Kreipe, V Teleanu, A Benner, H Döhner, M Grießhammer, K Döhner
Journal: Leukemia (2016)
Combined Effect Of Dnmt3a Loss-Of-Function and Idh2 neomorphic mutation Promotes Hematopoietic Malignancy
Authors: Xiaotian Zhang, Ting Zhou, Putluri Nagireddy, George Michailidis, Mira Jeong, Arun Sreekumar, Vivienne I. Rebel, Margaret A. Goodell
Journal: Blood (2013)
Detection of BCR-ABL Mutations in Patients with Chronic Myeloid Leukemia Treated with Imatinib. Experience of One Centre.
Authors: J. Valentin Garcia Gutierrez, Jesùs Odriozola, Javier Lopez, Pilar Herrera, Maria Calbacho, Marta Jimenez-Rolando, Maria Tenorio, Anabelle Chinea, Jose Garcia-Laraña
Journal: Blood (2009)
Interim safety analysis of a randomized phase III study evaluating pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line chemotherapy for metastatic breast cancer (MBC): The PELICAN study
Authors: N. Harbeck, S. Saupe, A. Kerber, H. J. Lueck, C. Jackisch, M. Untch, M. Schmidt, E. Jäger, S. Al-Batran
Journal: Journal of Clinical Oncology (2008)

12010 Background: MBC is still an incurable disease. Effective single agent chemotherapy is increasingly used in the frontline setting to lower toxicity and maintain patient’s quality of life (QoL). The phase III PELICAN trial was designed to evaluate efficacy and safety of first-line PLD (50 mg/m2, q28 days) vs. capecitabine (1,250 mg/m2 BID×14 days, q21 days) as approved dose for both agents. Methods: Pts with MBC were eligible. They received either PLD 50 mg/m2 iv every 28 days or capecitabine 1,250 mg/m2 orally twice daily for 14 days followed by a 7-day rest period (qd21) as a first line treatment. Toxicity was evaluated continuously, efficacy and quality of life every 3 months; cycles were repeated until disease progression or unacceptable toxicity. Results: The PELICAN trial is actively enrolling pts. 79 pts (PLD n= 40; capecitabine n=39) were analyzed for safety. Median age was 61 years (range, 35–80. Pts received a median of 4 cycles (1–20). Both drugs were associated with comparable rates of grade 1–3 hand foot syndrome (HFS) (PLD, 43%; capecitabine, 49%); capecitabine was associated with more diarrhea (35.9% v 5%) and more grade 3 or 4 thromboembolic events (7.7% v 0%). All other grade 3 or 4 toxicities affected less than 5% of pts in both arms. Altogether, 27 pts discontinued treatment: 15 for disease progression, 4 for toxicity, 2 died, and 6 for other reasons. Dose reductions related to HFS or diarrhea were documented in 34% of pts and treatment delay > 1 week in 19%. Serious adverse events were reported in 19 pts. Conclusions: These preliminary results showed no unanticipated toxicity. The toxicity observed was manageable and did not lead to treatment discontinuation. Thus, the IDMC recommended the continuation of patient accrual to the pre-set target of 346. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Essex Pharma, Roche
Targeted Gene Sequencing to Identify Polymorphisms in the Protein C and EPCR Genes in Patients with Unprovoked Venous Thromboembolism.
Authors: Cynthia M Wu, Dhruva J Dwivedi, Wasifa Zarin, Zakhar Lysov, John S Waye, Clive Kearon, Patricia Liaw
Journal: Blood (2009)
Industry sponsorship hits the headlines
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

Media focus on a sponsor of the RCGP conference has raised fresh questions about funding of medical meetings, Zosia Kmietowicz reports

The headlines after the first day of the Royal College of General Practitioners’ annual conference at the beginning of October were unexpected. Chair Maureen Baker’s speech to the 1630 registrants was largely overlooked in favour of a story about a flyer included in delegates’ bags from a company called Babylon, which offers consultations to patients through smart phones.

“GPs poached for private work,” was the headline in the Times , while the Daily Mail ’s declared “Doctors’ leaders urge them to earn £90k from private sessions online.” The Guardian ran the story under the headline, “GPs offered thousands of pounds to give private consultations via app.”

The stories suggested that GPs were being lured from the NHS with promises of £50-£60 an hour, or £90 000 (€100 000; $110 000) a year if they worked full time, to see private patients from their homes or usual workplace.

Babylon also sponsored a session at the conference on “using technology to improve healthcare on a global scale” and had its logo on the programme and on the RCGP website.

In a statement the RCGP said that Babylon was “working with the NHS in some areas to reduce pressure on GP surgeries by offering virtual consultations.”

It added: “At the moment, general practice in the UK is struggling, and we need to pull out all the stops to recruit as many GPs to the NHS as possible, and retain existing ones. But that is not to say we are in a position to close the doors to opportunities for our members.

“Babylon’s presence at the annual conference is in line with the college’s sponsorship policies.”

The college said that “commercial confidentiality” prevented it from disclosing …
GW26-e1352 Bivalirudin Versus Heparin Plus Glycoprotein IIb/IIIa Inhibitors in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: a Meta-Analysis of Randomized Controlled Trials
Authors: Jianbing ZHU, Junbo Ge
Journal: Journal of the American College of Cardiology (2015)
Closing the loop: 3C versus DNA FISH
Authors: Luca Giorgetti, Edith Heard
Journal: Genome biology (2016)

Chromosome conformation capture (3C)-based techniques have revolutionized the field of nuclear organization, partly replacing DNA FISH as the method of choice for studying three-dimensional chromosome architecture. Although DNA FISH is commonly used for confirming 3C-based findings, the two techniques are conceptually and technically different and comparing their results is not trivial. Here, we discuss both 3C-based techniques and DNA FISH approaches to highlight their similarities and differences. We then describe the technical biases that affect each approach, and review the available reports that address their compatibility. Finally, we propose an experimental scheme for comparison of 3C and DNA FISH results.
The Influence of Cytochrome P450 3A Gene Polymorphisms on Tacrolimus Concentrations in Hematopoetic Stem Cell Transplantation Patients.
Authors: Masahiro Ogasawara, Mizuha Kosugi, Satomi Matsuoka, Shinsuke Asamuma, Shinsuke Noguchi, Sirou Fujii, Akinori Wada, Shuichi Ota, Masanobu Nakata, Kiyotoshi Imai, Naoki Kobayashi, Yoshio Kiyama, Masaharu Kasai
Journal: Blood (2008)
EZH2 Is Either Mutated or Downregulated in Patients with Loss of Heterozygosity of Chromosome 7/7q and Leads to Epigenetic Dysregulation Via Histone H3K27.
Authors: Hideki Makishima, Shahper N Khan, Anna M Jankowska, Yuka Sugimoto, Zhenbo Hu, Venugopalan Cheriyath, Reda Mahfouz, Quteba Ebrahem, Sergei Vatolin, Yogen Saunthararajah, Mikkael A. Sekeres, Jaroslaw P Maciejewski
Journal: Blood (2011)
Association Between Changes in CMS Reimbursement Policy and Drug Labels for Erythrocyte-Stimulating Agents With Outcomes for Older Patients Undergoing Hemodialysis Covered by Fee-for-Service Medicare
Authors: Cunlin Wang, Robert Kane, Mark Levenson, Jeffrey Kelman, Michael Wernecke, Joo-Yeon Lee, Steven Kozlowski, Carmen Dekmezian, Zhiwei Zhang, Aliza Thompson, Kimberly Smith, Yu-te Wu, Yuqin Wei, Yoganand Chillarige, Qin Ryan, Chris Worrall, Thomas E. MaCurdy, David J. Graham
Journal: JAMA Internal Medicine (2016)

In 2011, the US Centers for Medicare & Medicaid Services (CMS) changed its reimbursement policy for hemodialysis to a bundled comprehensive payment system that included the cost of erythrocyte-stimulating agents (ESAs). Also in 2011, the US Food and Drug Administration revised the drug label for ESAs, recommending more conservative dosing in patients with chronic kidney disease. In response to concerns that these measures could have adverse effects on patient care and outcomes, the CMS and the FDA initiated a collaboration to assess the effect.
Evaluation of psychological distress, anxiety and depression in oncologic patients admitted to a medical oncology unit
Authors: B. Buralli, S. Manai, A. Camerini, C. Aiosa, L. Amadei, S. Donati, G. Tartarelli, C. Valsuani, O. Garrone, D. Amoroso
Journal: Journal of Clinical Oncology (2007)

19658 Background: psychological status influences patients’ compliance to treatments, quality of life and perhaps final outcome. Moreover, the screening for psychological disturbances may allow patients at risk to be identified so they can benefit from specific interventions. Methods: 133 consecutive unselected pts (76 F, mean age 63.7 ± 11.6 yrs) admitted to our Medical Oncology Unit were evaluated at hospital admittance. We employed the Italian validated version of the Hospital Anxiety Depression Scale (HADS) questionnaire, a self-administered questionnaire specifically developed to reveal states of distress (D), anxiety (A) end depression (DE) in non- psychiatric patients with an organic disease. Two cut-off values (7 and 11 points) to identify borderline (8–10 points) and probable clinically relevant cases (= 11 points) in A and DE scales were used. Scores between 15 and 21 were considered as borderline cases and &gt;21 were considered to be of clinical relevance in total D scale. Results: mean total D, A and DE levels were 16.5 ± 11.6, 7.8 ± 4.7 and 8.3 ± 5.3 respectively. Females showed higher levels than males for all parameters (D: 17.6 ± 9.5 vs 14.2 ± 8.1, p=0.031; A: 8.6 ± 4.9 vs 6.9 ± 4.2, p=0.035; DE: 9.1 ± 5.6 vs 7.3 ± 4.7, p=0.06ns). Age-related subgroup analysis demonstrated a trend towards higher A scores in =40 yrs pts vs total population (11.0 ± 3.0 vs 7.8 ± 4.7, p=0.08ns) and significantly higher D and DE values in =80 yrs pts (22.6 ± 11.3 vs 16.2 ± 9.1, p=0.05 and 13.0 ± 6.6 vs 8.3 ± 5.3, p=0.025 respectively). Regression analysis showed in females a significant direct correlation between age - D (r = +0.46, p = 0.048) and age - DE (r = +0.62, p = 0.0019) and in males a significant inverse correlation between age - D (r = -0.52, p = 0.04), age - A (r = -0.45, p = 0.05) and a clear trend between age - DE (r = -0.42, p = 0.07ns). Conclusions: the study population presented with borderline admittance D, A and DE values. In particular, young males respect to A and old women respect to D and DE represent higher risk groups for future development of psychological abnormalities complicating disease treatment. Prospective studies are ongoing to evaluate the impact of pts recovery and/or treatment on psychological parameters. No significant financial relationships to disclose.