tbuckley/cabot-search huggingface dataset:
Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas
Authors: Yuxuan Wang, Simeon Springer, Carolyn L. Mulvey, Natalie Silliman, Joy Schaefer, Mark Sausen, Nathan James, Eleni M. Rettig, Theresa Guo, Curtis R. Pickering, Justin A. Bishop, Christine H. Chung, Joseph A. Califano, David W. Eisele, Carole Fakhry, Christine G. Gourin, Patrick K. Ha, Hyunseok Kang, Ana Kiess, Wayne M. Koch, Jeffrey N. Myers, Harry Quon, Jeremy D. Richmon, David Sidransky, Ralph P. Tufano, William H. Westra, Chetan Bettegowda, Luis A. Diaz, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Nishant Agrawal
Journal: Science Translational Medicine (2015)

Tumor DNA in saliva and plasma can provide a noninvasive biomarker for head and neck squamous cell carcinoma.
Alternatives Assessment Frameworks: Research Needs for the Informed Substitution of Hazardous Chemicals
Authors: Molly M. Jacobs, Timothy F. Malloy, Joel A. Tickner, Sally Edwards
Journal: Environmental Health Perspectives (2015)

Given increasing pressures for hazardous chemical replacement, there is growing interest in alternatives assessment to avoid substituting a toxic chemical with another of equal or greater concern. Alternatives assessment is a process for identifying, comparing, and selecting safer alternatives to chemicals of concern (including those used in materials, processes, or technologies) on the basis of their hazards, performance, and economic viability.The purposes of this substantive review of alternatives assessment frameworks are to identify consistencies and differences in methods and to outline needs for research and collaboration to advance science policy practice.This review compares methods used in six core components of these frameworks: hazard assessment, exposure characterization, life-cycle impacts, technical feasibility evaluation, economic feasibility assessment, and decision making. Alternatives assessment frameworks published from 1990 to 2014 were included.Twenty frameworks were reviewed. The frameworks were consistent in terms of general process steps, but some differences were identified in the end points addressed. Methodological gaps were identified in the exposure characterization, life-cycle assessment, and decision-analysis components. Methods for addressing data gaps remain an issue.Greater consistency in methods and evaluation metrics is needed but with sufficient flexibility to allow the process to be adapted to different decision contexts.Although alternatives assessment is becoming an important science policy field, there is a need for increased cross-disciplinary collaboration to refine methodologies in support of the informed substitution and design of safer chemicals, materials, and products. Case studies can provide concrete lessons to improve alternatives assessment.
Phase 1 first-in-human dose escalation study of cp-751,871, a specific monoclonal antibody against the insulin like growth factor 1 receptor
Authors: M. Lacy, M. Alsina, C. L. Melvin, L. Roberts, D. Yin, J. F. Petersen, A. Birgin, S. Poutney, A. Sharma, A. Gualberto
Journal: Journal of Clinical Oncology (2006)

7609 Background: Multiple lines of evidence indicate that the Insulin Like Growth Factor 1 Receptor (IGF-1R) plays a key role in the progression of multiple myeloma (MM). IGF-1 is a growth factor for MM cells. It promotes survival to the cytotoxic effects of chemotherapy in animal models of MM and its blood levels has been shown to correlate with those of paraprotein in MM patients. CP-751,871, a fully human monoclonal antibody, is a highly specific and potent inhibitor of the autophosphorylation of IGF-1R. Methods: Based on its mechanism of action and the potential relevance of IGF-1R in MM, a Phase 1 First-in-Human dose escalation study was initiated with the objective to define the safety and tolerability, and to characterize the pharmacokinetic and pharmacodynamic properties of CP-751,871 in this patient population. Patient’s eligibility included previously treated multiple myeloma in relapse or refractory phase and/or less than complete remission following autologous stem cell transplant or tandem transplant. Results: Following informed consent and screening, 10 dose-escalation cohorts of patients received from 0.025 to 10 mg/kg of CP-751,871 by iv infusion on Day 1 of 4-week cycles. In patients with a suboptimal response to CP-751,871 alone, oral dexamethasone was added to the treatment regimen. Patients received up to 14 cycles of CP-751,871 therapy, alone or in combination with dexamethasone. No dose limiting toxicities have been identified to date. Plasma CP-751,871 exposure increases with dose, and the pharmacokinetic characteristics are consistent with target-mediated disposition. Pharmacodynamic measurements indicate complete target saturation by CP-751,871 for the complete length of the dosing period. One near CR and 2 PR in combination with dexamethasone have been reported. Conclusions: These data indicate that CP-751,871 is well tolerated and may constitute a therapeutic approach for patients with multiple myeloma. [Table: see text]
The effect of elotuzumab on natural killer (NK) cell function against multiple myeloma (MM).
Authors: S. M. Collins, C. E. Bakan, Y. Alghothani, H. Kwon, B. Balasa, G. Starling, A. Rice, D. M. Benson
Journal: Journal of Clinical Oncology (2011)

2572 Background: Elotuzumab (Elo), an anti-CS1 monoclonal antibody (mAb) in development for MM, exerts anti-MM effects via NK cell-mediated ADCC. CS1 is also expressed on NK cells. We provide data to suggest that Elo may enhance NK cell cytotoxicity via mechanisms beyond ADCC. Methods: Primary cells were procured under IRB-approved protocols. Interferon-gamma (IFN-g) and granzyme B (GrB) production were measured by ELISPOT, NK92 cytotoxicity was determined by chromium release. Flow cytometry characterized NK cell subsets and effects of Elo on NK cell activation. Elo, Elo-G2M3 (non-CD16 binding), and isotype mAbs were from Abbott Biotherapeutics Results: Pts with advanced MM have proportionally fewer cytotoxic CD56dim NK cells in peripheral blood (22%+/-2) vs. pts with early MM (69%+/-10, n=8, p=0.005). While Elo increased CD69 expression on healthy donor NK cells (22.8%+/-7) vs. isotype (4.8% +/- 3, n=5, p = 0.01), no increase in NK cell cytotoxicity against autologous NK cells was observed. Across a range of effector:target (E:T) ratios, Elo (and G2M3 at higher E:Ts) enhanced NK cell IFN-g production (e.g., E:T 25:1, control = 86+/-6, G2M3= 109+/-4, Elo = 275+/-12, p = 0.0001, all pair-wise comparisons significant) and GrB production (e.g., E:T 50:1, control = 113+/-11, G2M3 = 179+/-6, Elo = 331+/-25, p=0.0001, all pair-wise comparisons significant). Elo increased CD107a expression (9.3%+/-2.2) on NK cells in MM bone marrow aspirates vs. isotype control (5.8%+/-0.5, n=3, p = 0.04). Elo also enhanced the killing of CS1+ targets by CD16- NK92 cells. Conclusions: Elo activates NK cells and promotes cytotoxicity via IFN-g and GrB degranulation specifically directed against MM targets, observations confirmed by increased CD107a expression on NK cells in bone marrow of pts with MM. Elo facilitates NK cell function against MM by mechanisms in addition to ADCC based on 1) G2M3 enhancement of IFN-g and GrB production against MM cells, 2) Elo induced CD69 expression independent of presence of MM targets and 3) Elo-enhanced killing of CS1 expressing target cells by a CD16 negative NK cell line. Elo does not induce cytotoxicity against NK cells.
Cure of Murine Leukemia With Drug and Interferon Treatment
Authors: M. A. Chirigos, J. W. Pearson
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Cure of Murine Leukemia With Drug and Interferon Treatment Get access M. A. Chirigos, M. A. Chirigos Search for other works by this author on: Oxford Academic PubMed Google Scholar J. W. Pearson J. W. Pearson Viral Leukemia and Lymphoma Branch, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Md. 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 4, October 1973, Pages 1367–1368, https://doi.org/10.1093/jnci/51.4.1367 Published: 01 October 1973 Article history Received: 25 June 1973 Accepted: 17 July 1973 Published: 01 October 1973
Complete blood count may provide risk stratification for survival and AML transformation in CMML
Authors: J. Cerny, N. Galili, Q. Liu, D. Devuni, K. Hassan, R. Upadhyay, M. Mumtaz, M. Mehdi, A. Raza
Journal: Journal of Clinical Oncology (2007)

17502 We performed a retrospective analysis of 120 patients with CMML (98 de novo CMML and 22 evolving from MDS) to examine clinical features that may influence survival and AML transformation. Univariate analysis showed low hemoglobin level; WBC &gt; 13,000, platelet count &lt; 50,000 and abnormal cytogenetics as poor prognostic features. Univariate analysis also determined that BM blasts &gt;5% and Int2/High IPSS were associated with higher rates of AML but IPSS could not be used for survival assessment. Multivariate analysis showed hemoglobin &lt; 12 g/dL, older age, abnormal cytogenetics as risk factors for shorter survival; older age, male sex, low platelet count, BM blasts &gt; 5%, lymphocyte and monocyte counts were independent risk factors for AML transformation. Previous attempts to devise prognostic scoring systems for CMML have incorporated both peripheral blood and bone marrow features. We have used hemoglobin, lymphocyte count and platelet count to generate 3 prognostic scoring systems, which differed by severity of thrombocytopenia. Score 1 (&gt;100, 50–100, &lt;50) identified 3 different risk groups (low, intermediate, and high) with median OS: not reached (n/a), 18, and 9 months for all CMML patients (p&lt;0.0001) as well as for the de novo CMML patients (p&lt;0.0001). Score 2 (&gt;50, &lt;50) divided patients into 3 risk groups (low, intermediate, and high) with median OS: n/a, 19 and 10 months for all CMML (p=0.0002) versus n/a, 28 and 11 months for de novo CMML patients (p=0.0011). Score 3 (&lt;100, &gt;100) separated all CMML (p=0.0073) and de novo CMML patients (p=0.0054) into 2 risk groups (high, low) with median time to AML 53 months and n/a. In conclusion we suggest three new scoring systems for CMML patients that can be easily calculated after an initial CBC. Scores 1 and 2 help to assess survival while score 3 indicates risk for AML transformation. *Acknowledgements: This work has been partially supported by the AMA Foundation Seed Grant Research Program 2006. No significant financial relationships to disclose.
Cost utility analysis of nab-paclitaxel weekly or q3w compared with docetaxel q3w as first-line therapy in metastatic breast cancer (MBC).
Authors: G. Dranitsaris, M. Perayre Badia, A. Clopes, M. Fernández Ortega, M. Rey Salido
Journal: Journal of Clinical Oncology (2010)

e16545 Background: In Spain, the standard of care for the treatment of HER2-negative MBC patients previously treated with anthracyclines is a q3w schedule of docetaxel or weekly paclitaxel. In many European countries, a nanoparticle albumin-bound (nab) formulation of paclitaxel is now available. A randomized phase II trial comparing nab-paclitaxel 100 or 150 mg/m2 weekly 3 out of 4 and nab-paclitaxel 300 mg/m2 q3w to docetaxel 100 mg/m2 q3w showed improved progression-free survival and reduced toxicity with the former regimens (Gradishar, 2009). To measure the economic value of the nab-paclitaxel regimens, a cost utility analysis was conducted from the perspective of the Spanish health care system. Methods: The current study extracted data captured during the randomized trial. Health care resource data contained within the database were quantified using Spanish cost estimates. This consisted of costs for chemotherapy, drug delivery, monitoring, supportive care drugs, and hospitalization due to toxicity. Health state utilities were then obtained from interviewing 25 Spanish oncology nurses and pharmacists using the Time Trade-off technique. Results: Hematopoietic growth factor use, hospital days for side effects management, and toxicity-induced protocol discontinuations were higher in the docetaxel group. When all of the cost components were quantified, patients in the nab-paclitaxel 100 mg/m2 weekly and 300 mg/m2 q3w groups had comparable costs to the docetaxel control (€16,163 vs. €15,621 vs. €13,839; p = NS). The nab-paclitaxel 150 mg/m2 weekly arm had a significantly higher overall cost at €26,464 per course, but was associated with a significant improvement in progression-free survival compared to docetaxel. As alternatives to docetaxel, the incremental cost per QALY gained with nab-paclitaxel 150 mg/m2 weekly and 300 mg/m2 q3w was €11,500 and €43,800 respectively. Conclusions: nab-paclitaxel (weekly or q3w) could be considered an economically sound alternative to docetaxel q3wk for the treatment of HER2-negative MBC patients previously exposed to anthracyclines. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abraxis BioScience Abraxis BioScience Abraxis BioScience
Gemcitabine plus carboplatin in recurrent and advanced breast cancer: A phase II trial
Authors: J. A. Silva, L. M. Perez Michel, D. Gallardo Rincon
Journal: Journal of Clinical Oncology (2004)

877 Background: Gemcitabine is an active drug in breast cancer: 37% of responses as first line, 26% as a second line and 18% as tirad line; The responses with Gemcitabine plus cisplatin is patients with MBC is: 40% to 80%. Carboplatin has not been identified as active drug in breast cancer, however gemcitabine hs an wide synergism with this drug. Methods: The aim of this study was to evaluate the efficacy and security of the chemotherapy with gemcitabine and carboplatin in recurrent breast cancer. All patients had clinically and by scan CT, measurable disease. Treatment: Gemcitabine 1000 mg/m2 days 1 and 8, Carboplatin AUC 5 day 1, Cycles repeated q21 days as blood count permitted until limited toxicity or progression. Results: 19 patients were treated with palliative chemotherapy with GC, and there were 69 courses of chemotherapy. All pts received anthracyclines, FAC 15 pts, Tac 1 pt and 3 pts combined with taxanes in adjuvant setting; all received radiotherapy after adjuvant chemotherapy and all received also hormonal therapy in adjuvant setting. All pts received taxanes in recurrence and between 2 and 4 chemotherapy schedules that included: capecitabine, other taxanes, vinorelbine, 5FU and cisplatin. Median age was 44.5 years. 15 pt had ductal adencarcinoma and 2 pts had lobulillar carcinoma. . Stage II: 6 patients and stage III-IV: 12 patients; median follow-up was 5.2 (3.4–10.8 mo). Objective Responses (OR) were presented in 4 pt (21.5%); CR 2 pt, PR 2 pt and Stable disease 8 pts; Progression disease (PD) in 7 pts (31.3%); the responses were two locally and two more in the metastatic disease (hepatic). Median overall survival was 7.5 mo. The current status is 4 pts alive without tumoral activity (18.7%), 12 pts alive with tumoral activity (62.6%), and 3 dead pts with tumoral activity (18.7%). Related to toxicity anemia was presented in 4 pts (5.79%), Leucopenia in 3 pts (4.34%), neutropenia in 4 pts (5.79%) and thrombocytopenia in 1 pt (1.44%). Conclusion: Gemcitabine plus carboplatin is an active combination (11 OR), this scheme is of an easy administration, and very well tolerated in patients with metastatic and recurrent breast cancer, must be considered as an option in the metastatic setting. No significant financial relationships to disclose.
EGFR and phospho-EGFR expression in colorectal cancer patients and impact on survival
Authors: J.-P. Spano, A. T. Hbibi, C. Lagorce, G. Desguetz, R. Benamouzig, O. Rixe, J.-F. Morere, A. Martin, R. Fagard
Journal: Journal of Clinical Oncology (2005)

3690 Background: Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, especially in colorectal cancer (CRC). Blocking EGFR activation represents an innovative strategy in patient care but additional efforts are needed to establish better predictors of the efficacy of EGFR inhibitors. In the present study, we evaluated EGFR and activated EGFR, such as phospho-EGFR, by immunohistochemistry (IHC) and tissue microarrays (TMA) in CRC patients and we analyzed their relationships with various clinical and histological parameters and survival. Methods: Tumor blocks were obtained from CRC patients and arranged in a tissue microarray (Beecher Instruments). Four biopsies, 0.6 mm in diameter, were obtained from each donor block. IHC was performed using anti-EGFR anti-bodies (Zymed, USA) and anti-phospho-EGFR anti-bodies (tyr 845, tyr 992, tyr 1045, tyr 1068). A composite score was used to define patients with low or high EGFR and phospho-EGFR levels expression (0–9). Univariate tests and multivariate Cox proportional hazards model were applied for data analysis. Results: EGFR expression was detected in 78% of 126 CRC patients. Phospho-EGFR tyr 845 was found in 100% of the CRC cases, with a score inferior to 6 in 40% of cases and superior to 6 in 60% of cases. Phospho-tyr 992, 1045, 1068 were respectively found in 23%, 0%, and 0% in the CRC cases. The phosphor-EGFR tyr 845 was mainly located in the nucleus. No relationship was found between EGFR and phospho-EGFR levels expression and other clinicopathological variables study, either with overall survival. Conclusions: EGFR is expressed in CRC patient population such as some activated EGFR, tyr 845 and tyr 992. Thus linking molecular diagnostics to identify patients where the target is activated would be necessary to translate these findings into targeted therapeutic approaches.These findings could therefore offer an opportunity to test the efficacy of EGFR inhibitors in such setting. Other biomarkers from the EGFR downstream signaling pathway are still evaluated in our CRC patient population and will be presented. No significant financial relationships to disclose.
HeLa-Like Marker Chromosomes and Type-A Variant Glucose-6-phosphate Dehydrogenase Isoenzyme in Human Cell Cultures Producing Mason-Pfizer Monkey Virus-Like Particles2
Authors: W. A. Nelson-Rees, V. M. Zhdanov, P. K. Hawthorne, R. R. Flandermeyer
Journal: JNCI Journal of the National Cancer Institute (1974)

A virus similar to the Mason-Pfizer monkey virus (M-PMV) has been discovered in certain human cell lines by workers in the United States. It was extensively studied in cell line AO. Other laboratories have also discovered this virus or similar viruses in certain human cells. Since this virus had been isolated in 1970 from only a rhesus monkey mammary adenocarcinoma, it was deemed necessary to study these cells for species origin and possible donor characteristics. We examined the chromosomes and glucose-6-phosphate dehydrogenase (G6PD) mobility patterns of AO and 5 other cell lines [H.EP.#2 (clone), J96, DAPT, T-9, and CaOV]. Conventional Giemsa staining revealed hypotriploidy for human chromosomes in all cells of all lines. Quinacrine fluorescence indicated the absence from all cells of a Y chromosome either alone or in translocation with another chromosome. A trypsinGiemsa technique for chromosome banding revealed 1) some marker chromosomes unique to each cell line and 2) several marker chromosomes common to all cell lines, as well as to our culture of HeLa cells and to other cultures of HeLa cells reported in the literature. G6PD mobility for all lines was of the type-A variant also characteristic of HeLa cells. We concluded that, while certain chromosomal differences existed between these 6 cell lines and HeLa cell cultures, their possession, in common with HeLa, of an isoenzyme mobility pattern for G6PD and of unique marker chromosomes clearly established their derivation from the HeLa cell line.
Smoking cessation process
Authors: Ika Pesic, Nada Lazovic, Branislav Gvozdenovic
Journal: European Respiratory Journal (2012)

Introduction:  Serbia has ratified the Law on protection from exposure to tobacco smoke. The Law regulates all working and public places to be a smoke-free.  Objective:  Consideration of the effects of smoking cessation by gender, education and the employment status in 2010 when the Law is ratified.  Methods: The analysis of data was performed by means of t-test for independent samples and analysis of variance (ANOVA).  Results:  A total of 2.030 smokers were interested for the smoking cessation program in the Serbian counselings. Of these, 1.489 smokers attended the program, and 1.134 (75.7%) finished it. The Law motivated 187 (16.5%) smokers to participate in the cessation program. There were 34.6% men (M) and 65.4% women (W). The majority of subjects (59.9%) had the secondary school education 59.9%. There were 64.7% employed smokers in total. Regarding the gender, women (40.4%) were more successful than men (32.7%). Women with the secondary school and those not employed (60.7%, 30.7% respectively) were significantly more successful than men (43.7%, 21.9% respectively) (p   Conclusion : The biggest number of employed subjects who attended the smoking cessation program can be associated with the ratification of the Law that regulates the working places without the tobacco smoke. On that way the Law initiated the initiative among the employed persons for the smoking cessation.
SKI-606, a novel Src kinase inhibitor, blocks migration and invasion of human breast cancer cells
Authors: Adina Vultur, Ralf Buettner, Claudia Kowolik, David Smith, Frank Boschelli, Richard Jove
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3251 

Src family kinase (SFK) activity is elevated in human breast cancer and is often associated with aggressive disease. Numerous studies point to the central roles of SFKs, notably c-Src, in regulating multiple signaling pathways involved in proliferation, adhesion, motility, and survival of human tumors, thus implicating c-Src as a potential target for cancer therapy. We examined the effects of SKI-606, a novel, orally bioavailable, highly-selective Src family kinase inhibitor, on human breast cancer cells in order to assess its potential for breast cancer treatment. Importantly, our results show that SKI-606 caused a dramatic decrease in cell motility and invasion of human breast cancer cell lines with an IC50 of ~250 nM. These changes were accompanied by an increase in cell-to-cell adhesion, membrane localization of beta-catenin, and a decrease in matrix metalloproteinase-9 activity. Contrary to expectations, inhibition of Src activity did not coincide with inhibition of cell proliferation and survival. Studies of Src/Yes/Fyn knockout cells with restored c-Src provide genetic evidence that the mechanism of action of SKI-606 depends on targeting c-Src. Analysis of downstream effectors of c-Src revealed that SKI-606 inhibits the phosphorylation of focal adhesion kinase (FAK), proline-rich tyrosine kinase 2 (Pyk2) and Crk-associated substrate (p130CAS). Our findings indicate that SKI-606 inhibits signaling pathways involved in controlling tumor cell motility and invasion, suggesting that SKI-606 is a promising new therapeutic agent.
Apneic Oxygenation for Intubation in the Critically Ill. Let's Not Give Up!
Authors: Audrey De Jong, Samir Jaber
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not.The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Apneic Oxygenation for Intubation in the Critically Ill.Let's Not Give Up!