tbuckley/cabot-search huggingface dataset:
Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538).
Authors: Mario Sznol, Harriet M. Kluger, F. Stephen Hodi, David F. McDermott, Richard D. Carvajal, Donald P. Lawrence, Suzanne Louise Topalian, Michael B. Atkins, John D. Powderly, William Howard Sharfman, Igor Puzanov, David C. Smith, Jon M. Wigginton, Georgia Kollia, Ashok Kumar Gupta, Jeffrey Alan Sosman
Journal: Journal of Clinical Oncology (2013)

CRA9006^ The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Saturday, June, 1, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Dehalogenase genes of Pseudomonas putida PP3 on chromosomally located transposable elements.
Authors: J H Slater, A J Weightman, B G Hall
Journal: Molecular Biology and Evolution (1985)

Pseudomonas putida PP3 utilizes halogenated alkanoic acids (HAA) such as 2,2-DCPA as its sole carbon and energy sources. Spontaneous HHA- mutants, isolated by selection for resistance to the toxic analogs monochloroacetic acid and dichloroacetic acid, arose at frequencies several orders of magnitude higher than expected for spontaneous mutations. Analysis of the five classes of mutants isolated suggested that the dehalogenase and HAA permease genes were on chromosomally located transposable elements and that the spontaneous mutations involved excision of these elements. This suggestion was confirmed by the observation that one of the elements can transpose to a target DNA molecule. The frequency of the excision event was strongly influenced by environmental conditions. Possible relationships between expression of cryptic genes and their location on transposable elements are discussed.
Prednisolone Sensitivity and Cytology of Viable Lymphocytes as Tests for Chronic Lymphocytic Leukemia2
Authors: Robert Schrek
Journal: JNCI Journal of the National Cancer Institute (1964)

The sensitivity in vitro of blood lymphocytes to prednisolone (11β,17,21 -trihydroxypregna-1,4-diene-3,20-dione) is proposed as a diagnostic aid in chronic lymphocytic leukemia. Tests were done on 31 patients with chronic lymphocytic leukemia or lymphosarcoma in leukemic phase, on 11 patients with absolute lymphocytosis, and on 50 control persons with normal hemograms. For the test, purified suspensions of blood lymphocytes were incubated with and without prednisolone (1 μg/ml) for 7 days. The number of viable lymphocytes were counted in the suspensions before and after incubation. The sensitivity of the lymphocytes was expressed by the percent effect produced by the prednisolone on the number of viable lymphocytes after 7 days of incubation. Tests showing 60 percent effect or more were considered positive and less than 40 percent negative. Positive tests were obtained in 25 of 31 patients with leukemia, in 2 of 11 patients with lymphocytosis, and in none of 50 individuals with normal hemograms. Negative tests were obtained in 3 of 31 patients with leukemia, in 44 of 50 control individuals, and in 8 of 11 patients with lymphocytosis. It is concluded that a positive sensitivity test indicated leukemic lymphocytes but a negative test did not exclude leukemia. Certain cytologic abnormalities seen by phase microscopy in viable lymphocytes before and after incubation were considered as indicative of leukemia. These abnormalities included prominent chromatin masses adherent to the nuclear wall, large, dark nucleoli, irregularity in the shape of cells, and thin, elongated cytoplasmic projections. These cytologic characteristics were present in most cells of 21 of 31 leukemic patients, in 2 of 11 patients with lymphocytosis, and in none of the control individuals.
Acute radiation esophagitis in a phase I dose-escalation trial evaluating helical tomotherapy for inoperable non-small cell lung cancer (NSCLC)
Authors: G. M. Cannon, H. A. Jaradat, W. A. Tome, D. Khuntia, M. P. Mehta, S. M. Bentzen
Journal: Journal of Clinical Oncology (2007)

7694 Background: In an attempt to improve the poor local control in patients with locally advanced and medically inoperable lung cancer we investigated helical tomotherapy as a means to decrease radiation dose to critical normal structures while escalating tumor dose. Methods: Thirty-six patients with Stage I-IV NSCLC requiring definitive radiotherapy and judged not to be surgical candidates due to medical comorbidities or advanced tumor stage were enrolled in this phase I trial. Chemotherapy was given sequentially but not allowed concurrently. Pts were placed in 1 of 4 dose-per-fraction bins, all treated for 25 fractions, with dose per fraction ranging from 2.28 to 3.22 Gy. Bins were calculated to yield normalized total dose (NTD) equivalents in 2 Gy fractions of 60–100 Gy. Dose escalation limiting constraints included esophageal maximum NTD, lung NTD mean, and esophageal effective volume (V eff ). Radiotherapy was limited to the primary site and clinically proven or suspicious nodal regions. Elective nodal irradiation (ENI) was not performed. A graded-response logistic regression analysis was performed to identify dosimetric and clinical factors associated with esophagitis. Results: No grade 3 (CTCAE v3.0 and RTOG) acute esophageal toxicities were observed. Only 6 patients (16.7%) required narcotic analgesia (RTOG gr. 2 toxicity). Average mean NTD dose to the esophagus (D mean )=15.3 Gy. Average volume of the esophagus receiving NTD 55 Gy (V 55 )=3.65%. Both D mean and V 55 were significantly associated with the grade of esophagitis, with P- values of 0.018 and 0.010, respectively. In this limited series, there was no significant effect of sequential chemotherapy, in agreement with previous studies. Conclusions: 1) Acute esophageal toxicity was minimal despite dose escalation via helical tomotherapy for inoperable NSCLC cancer. 2) The observed significant associations between V 55 , D mean , and grade of esophagitis validate improved dose distribution as a strategy to permit radiation dose escalation. Pending acceptable rates of radiation pneumonitis the addition of concurrent chemotherapy is anticipated. Supported by NIH Grant CA-88960. No significant financial relationships to disclose.
指南 抗生素在自限性呼吸道感染初级治疗中的使用：MCE指南概要
Authors: Toni, Tan, Paul, Little, Tim, Stokes, 张伟娟, 代华平
Journal: BMJ (2009)

为什么阅读这个概要？ 抗生素可能无益于大部分呼吸道感染的初始治疗。呼吸道感染大多数具有白限性，如果不使用抗生素，并发症可能极少发生。然而，在初始治疗的所有抗生素使用中，呼吸道感染就占了60％，抗生素的使用方法在普通临床实践中多种多样，而在高年资处方医师的实践中并没有明显获益的证据。
AIDS and non-Hodgkin's lymphoma: a pre-pre-B-cell monoclonal lymphoma versus a novel mechanism of polyclonality?
Authors: M Seiden, J Sklar
Journal: Journal of Clinical Oncology (1992)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1992.10.10.1650 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 1403043 AIDS and non-Hodgkin's lymphoma: a pre-pre-B-cell monoclonal lymphoma versus a novel mechanism of polyclonality? M SeidenxM SeidenSearch for articles by this author , J SklarxJ SklarSearch for articles by this author https://doi.org/10.1200/JCO.1992.10.10.1650 PDF "AIDS and non-Hodgkin's lymphoma: a pre-pre-B-cell monoclonal lymphoma versus a novel mechanism of polyclonality?." Journal of Clinical Oncology, 10(10), pp. 1650–1651© 1992 by American Society of Clinical Oncology
A tertiary cancer center experience with yttrium-90 radioembolization in hepatocellular carcinoma.
Authors: Kerry Schaffer, Marcus Smith Noel, Aram F. Hezel, Alan W. Katz, Ashwani Sharma, Andrea Baran, Gregory Clayton Connolly, Mohamedtaki Abdulaziz Tejani
Journal: Journal of Clinical Oncology (2015)

443 Background: Local-regional radioembolization with Yitrium-90 (Y-90) has become standard practice for patients with hepatocellular carcinoma (HCC) either as a bridge to transplant, or for local disease control. Outcomes data in the United States are limited and here we review our institutional experience with Y-90 radioembolization. Methods: We retrospectively reviewed charts from 70 patients with HCC who were treated with Y-90 from May 2010- January 2014. Clinical variables including Child-Pugh class and CLIP score were extracted from patient records. The Cox proportional hazards model was used to determine prognostic factors, and Kaplan-Meier curves were used to determine PFS and OS. Results: Median age was 61 (range 43-82), 79% Caucasian, 84% male, and 79% Child-Pugh class A. Median progression free survival (PFS) was 8.4 months (95% CI 6-10.7) and overall survival (OS) was 14.2 months (95% CI 9.7-21). Overall survival significantly differed by Child -Pugh score (p= 0.009), CLIP score (p=0.003), and presence of portal vein thrombosis (PVT) (p=0.0384), based on the log-rank test comparing Kaplan-Meier curves. Using univariate Cox proportional hazards models, both elevated baseline AFP, measured on a log scale (HR 1.79, 95% CI 1.32-2.43, p=0.0002) and post Y-90 treatment with sorafenib (HR=2.30, 95% CI 1.07-4.95, p=0.03) were associated with worse mortality. Elevated AFP (HR 2.45, 95% CI 1.73-3.47, p&lt;0.0001) and Child-Pugh score of B (HR 4.83, 95% CI 2.23-10.43, p&lt;0.0001) were associated with worse mortality in a multivariate Cox model adjusting for age and ethnicity. Furthermore, AFP values were significantly higher in the 10 patients who died within 4 months of Y-90 (p=0.001), and significantly lower in 7 patients who eventually received a liver transplant (p=0.0002). Conclusions: In patients undergoing treatment with Y-90 radioembolization, Child-Pugh class, CLIP score, presence of PVT, baseline AFP, and sorafenib post Y-90 were significantly associated with overall survival. Median PFS and OS data in this institutional cohort are encouraging. Further prospective studies on Y-90 treatment for HCC are warranted.
Serine/Threonine Kinase MLK4 Determines Mesenchymal Identity in Glioma Stem Cells in an NF-κB-dependent Manner
Authors: Sung-Hak Kim, Ravesanker Ezhilarasan, Emma Phillips, Daniel Gallego-Perez, Amanda Sparks, David Taylor, Katherine Ladner, Takuya Furuta, Hemragul Sabit, Rishi Chhipa, Ju Hwan Cho, Ahmed Mohyeldin, Samuel Beck, Kazuhiko Kurozumi, Toshihiko Kuroiwa, Ryoichi Iwata, Akio Asai, Jonghwan Kim, Erik P. Sulman, Shi-Yuan Cheng, L. James Lee, Mitsutoshi Nakada, Denis Guttridge, Biplab DasGupta, Violaine Goidts, Krishna P. Bhat, Ichiro Nakano
Journal: Cancer Cell (2016)
Paclitaxel (T)-ifosfamide (I)-carboplatin (Cb) (TICb) combination in advanced gynecologic malignant mixed Mullerian tumors (MMMT)
Authors: C. Kosmas, N. Mylonakis, N. Malamos, G. Tsakonas, A. Gassiamis, G. Soukouli, N. Tsavaris, A. Karabelis
Journal: Journal of Clinical Oncology (2005)

5125 Background: MMMTs of the uterus and adnexa represent aggressive gynecologic malignancies with a high rate of locoregional and distant failure. For that reason we evaluated the TICb combination in patients with advanced MMMTs. Methods: Female patients with advanced MMMTs [stages III-IV and relapses after surgery (Sx) ± radiotherapy (RT)], WHO-PS 0–2, no prior chemotherapy for systemic disease, unimpaired hematopoietic and organ function were eligible. Chemotherapy was administered at the following doses; T: 175mg/m2, I: 2.0g/m2/day-days 1+2, and Cb at a target AUC=5 (Calvert’s formula) on day 2 after I. Prophylactic G-CSF was usually administered from day 3–7. Results: 17 patients with MMMTs of the uterus (n=13), tubes (n=2), or ovary (n=2) have entered so far: median age=63 (45–72), PS=1 (0–1), stages; III=14 (82%), IV=3 (18%), histologies; with homologous sarcoma component: 11, with heterologous component: 6. Prior treatment for locoregional included Sx: 16, Sx+RT: 4. Disease sites at diagnosis included; pelvic disease (mass): 6, pelvic/paraortic nodes: 7, peritoneal implants: 9, liver: 2, lung: 5, bone: 1, malignant pleural effusion: 4. Responses were as follows: 11/17 (65%) evaluable patients responded, with 6 complete responses (CR) and 5 partial responses (PR), while 4 had stable disease (SD), and 2 developed progressive disease (PD). The median response duration was 8 mo (4–24), median time-to-progression (TTP) 13 mo (4–22), while median overall survival (OS) has not been reached yet since most patients receive second-line therapy. Grade (Gr) 3/4 toxicities included; neutropenia 9/17 (53%)-with 6 developing Gr4 (≤7 days) and 18% of patients at least one episode of febrile neutropenia managed successfully, thrombocytopenia Gr3: 2/17 (12%) and Gr4 1/17 (6%), no Gr3 neuropathy, Gr1 CNS toxicity in 1, no renal toxicity, 8 Gr2 myalgias, and 3 Gr3 vomiting. Conclusions: In the present study, it appears that the TICb combination, yielded important activity with acceptable toxicity in females with advance MMMTs. The study is ongoing. No significant financial relationships to disclose.
Use of Radioactive Iodine for Thyroid Cancer and Risk of Second Primary Malignancy: A Nationwide Population-Based Study
Authors: Chung-Jen Teng, Yu-Wen Hu, San-Chi Chen, Chiu-Mei Yeh, Huey-Ling Chiang, Tzeng-Ji Chen, Chia-Jen Liu
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Radioactive iodine (RAI) is widely used for the treatment of thyroid cancers. However, information on associations between RAI dose and second primary malignancy (SPM) is lacking.
Demonstration, Purification, and Partial Characterization of Abnormal (HSL)&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt; Antigens in Stable Human Cell Lines&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: J CHARNEY, L L CORIELL
Journal: JNCI Journal of the National Cancer Institute (1964)

The existence of abnormal (HSL) human stable line antigens common to a number of stable human cell lines, but absent from normal human tissues and normal human diploid cell strains in tissue culture, has been demonstrated by agar gel microimmunodiffusion. HSL was detected in HeLa-SJ, HeLa-MBA, HeLa-S3, Chang conjunctiva, Syverton's embryo esophagus, Chang liver, and J-111. It was not detected in Henle's human intestine or Detroit-6. It was absent from two normal diploid strains, WI-38 and SJ-DHL, and was not found in a variety of concentrated extracts of fresh human organs. HSL was not associated with contamination by pleuropneumonia-like organisms (PPLO) of cell lines. The purest HSL preparations obtained from HeLa-SJ by ammonium sulfate fractionation yielded absorption spectra characteristic of protein and were inactivated by trypsin. Sephadex chromatography indicated a particle weight of approximately 150,000; HSL was not sedimented at 125,000 × g. In 0.02 M PO4 buffer, activity was virtually completely eliminated after 2 minutes at 50° C, 8 minutes at 45° C, or 80 minutes at 40° C. Preliminary studies with fluorescent anti-HSL globulin indicated that HSL was not a surface antigen; rabbit antisera to purified HSL fractions were not cytotoxic to Hela cells. The best preparations of HSL still contained a trace of common human antigen and appeared to consist of multiple components active in immunoprecipitation. Electrophoresis indicated the inhomogeneity of this material.
Analysis of MGMT promoter methylation status in high grade glioma patients with long term and conventional survival times: A retrospective study
Authors: M. Preusser, M. Hassler, K. Elandt, E. Gelpi, J. Hainfellner, M. Baur, C. Marosi
Journal: Journal of Clinical Oncology (2007)

2084 Background: Response to alkylating chemotherapy in patients with high grade gliomas (HGG) has been found correlated to epigenetic silencing of the DNA repair gene MGMT (O6-methylguanine-DNA methyltransferase) in the tumor tissue. Patients with HGG expressing a methylated MGMT promoter benefited from alkylating chemotherapy in terms of a prolonged survival as compared to patients with unmethylated MGMT promoter. Methods: Our study cohort comprised 47 patients with HGG, all treated with concomitant chemotherapy and radiotherapy in our institution. 23/47 patients (8 women, 15 men, aged 22.4–64.5 years, median 36.3) survived longer than 36 months (range of survival times 36–137 months, in median 46.9 months) and were defined as long term survivors (LS). 24/47 patients (5 women and 19 men, aged 18.3–73.3 years, median 47.7) with early tumor relapse who survived in median for 23.5 months were defined as HGG patients with conventional survival (CS). In all cases, we extracted DNA from formalin-fixed and paraffin-embedded tumor tissue samples. The methylation status of the MGMT promoter was determined by bisulfide modification of the DNA and methylation-specific polymerase-chain- reaction (MSP). MSP results were rated by 4 independent observers. Results: There was high interobserver agreement at interpretation of MSP results (range of kappa values: 0.71–0.87). Among LS, we found MGMT promoter methylation in 13/24 (81.5%) patients and an unmethylated MGMT promoter in 3 patients, whereas the MSP results were not interpretable in 7 patients of this patient subgroup. Among CS, we found promoter methylation in 16 patients (66.6%), unmethylated promoter in 6 patients and uninterpretable results in one patient. There was no statistically significant difference in MGMT promoter methylation rate between LS and CS. Conclusions: The proportion of gliomas with methylated MGMT promoter in this series is unexpectedly high, particularly for CS patients. Potential explanations for this finding are methodological differences due to the use of paraffin-embedded tumors instead of frozen tumor material as in most published series and a potential random accumulation of MGMT positive tumors in the patients with CS survival. No significant financial relationships to disclose.
The impact of gender and age in renal cell carcinoma: age is an independent prognostic factor in women but not men
Authors: A. J. Pantuck, T. Klatte, J. Patard, L. Cindolo, A. De La Taille, J. Tostain, J. Ferriere, C. Pfister, F. F. Kabbinavar, A. S. Belldegrun, D. J. George
Journal: Journal of Clinical Oncology (2008)

5091 Background: Renal cell carcinoma (RCC) occurs twice as often in men as in women; however, the influence of gender on stage, grade, subtype and survival has not been studied in detail. If this imbalance in RCC incidence was related to gender-specific hormone levels, age could be a further significant variable. Methods: This study included 5,654 patients treated by nephrectomy at 10 international academic centers. Differences in gender, age, T, N, and M stage, Fuhrman grade, and histological subtype were evaluated with chi- square and Student’s t-tests. Kaplan-Meier survival estimates and Cox proportional hazards models addressed the impact of gender and age on disease-specific survival (DSS). Results: Of the 5,654 patients, 3,777 (67%) were men and 1,877 (33%) were women. Generally, women presented at lower T stages (p<0.001), less frequently had distant metastases (p<0.001) and had lower grade tumors (p<0.001). In addition, women more frequently had clear-cell (87% vs. 82%) and less frequently had papillary RCC (7% vs. 12%) than men (p<0.001). As a group, women had a 19% reduced risk of death from RCC than men (HR 0.81, 95% CI 0.73–0.90, p<0.001). Interestingly, the survival advantage for women was present to the greatest degree in the age group <40 years (p=0.0136), was intermediate in women aged 40–59 (p<0.001), and disappeared in patients aged 60 years and older (p=0.248). Among women, age was an independent predictor of DSS in multivariate analysis (HR 1.011, 95% CI 1.004–1.019, p=0.004). In contrast, age was not related to prognosis in men. Conclusions: Among women, age is an independent prognostic factor of DSS with the risk of RCC-specific death increasing by 1% with each year increase in age. As a group, women present with less advanced tumors, leading to a 19% reduced risk of RCC-specific death compared with men. This survival difference is present only in patients aged <60 years, but disappears in older patients. Since this gender based survival difference is not related to T, N, M stage, ECOG PS, or histological subtype, the role of estrogen on the development and progression of RCC needs to be studied. If a true estrogen effect on RCC does exists then the potential for hormone-targeted therapy in women will also need to be investigated. No significant financial relationships to disclose.
Long-term survival analysis: Pirfenidone compared to standard care for the treatment of patients with idiopathic pulmonary fibrosis
Authors: Neil Roskell, Owain Saunders, Dawn Lee, Mark Fisher
Journal: European Respiratory Journal (2014)

Objectives: Idiopathic pulmonary fibrosis (IPF) is a rare, fatal lung disease. Pirfenidone is a novel treatment for IPF patients. This analysis sought to predict survival with pirfenidone compared to standard care using clinical trial data and the CPRD-GOLD database.

Methods: Pirfenidone patients (2403 mg/day) from the two phase 3 CAPACITY trials, including up to 7-years follow-up from the extension study RECAP, were included in the analyses [n=345]. Standard care patients in the CPRD-GOLD database were identified using IPF-related READ codes and used as a reference group [n=193]. Survival times were recorded from diagnosis with CPRD, and from randomisation with the CAPACITY trials. Therefore, CPRD survival times were adjusted using random-sampling of diagnosis to randomisation collected in the CAPACITY trials. The CPRD cohort was restricted to only include patients with an FVC>50%, as per the inclusion criteria of the CAPACITY trials, in an effort to ensure similar levels of impairment in lung function between the two cohorts. Median survival was calculated within each group using the Kaplan-Meier estimator. Mean survival was extrapolated using parametric survival modelling techniques.

Results: Median survival was 6.87-years with pirfenidone compared to 3.41-years with standard care. Using stratified Weibull models, mean survival was 9.25-years (95% CI: 7.37-11.73) with pirfenidone compared to 5.25-years (95% CI: 4.05-7.00) with standard care.

Conclusions: This analysis suggests that for IPF patients treated with pirfenidone, survival is increased relative to patients in standard care, acknowledging the limitations of cross data source comparisons.