tbuckley/cabot-search huggingface dataset:
Morphologic Character of Transforming Renal Cell Cultures Derived From Wistar Rats Given Dimethylnitrosamine2
Authors: Gordon C. Hard, R. Borland
Journal: JNCI Journal of the National Cancer Institute (1977)

The morphologic character of kidney cells during serial subculture following isolation from Wistar rats treated several hours to 1 week previously with a carcinogenic dose of dimethylnitrosamine (DMN; 60 mg/kg body weight following protein deprivation) was compared with the appearance of cultures derived from normal control rats. Apart from early signs of cell toxicity, cultures from DMN-treated rats appeared similar to those from untreated rats for the first four passages. Control cells underwent senescence usually by subculture 4, whereas the test cultures survived to express morphologic transformation (usually at subculture 5) as dense macroscopic colonies of piled up cells. In 18 of the 20 test cultures, the cell populations that persisted in continuous culture following expression of morphologic transformation were exclusively mesenchymal, closely resembling DMN-induced renal mesenchymal tumor cells in continuous culture. In the remaining 2 test cultures from DMN-treated rats, a persisting population of abnormal epithelium was present in addition to morphologically transformed mesenchymal cells. The occurrence of populations of altered mesenchymal and epithelial cells characterized by prolonged survival in vitro following isolation from rats shortly after treatment with a carcinogenic dose of DMN was believed to be related to the long-term induction in the rat kidney of a high incidence of mesenchymal tumors and a lower incidence of cortical epithelial tumors by the same dose schedule.
Impact of capecitabine-related toxicities on chemotherapeutic dose delivery in colorectal cancer
Authors: J. Ho, S. Gill
Journal: Journal of Clinical Oncology (2008)

4101 Background: Capecitabine is considered a well tolerated systemic chemotherapy. This study examines the dose-limiting toxicities of capecitabine and its impact on dose delivery in general population clinical practice. Methods: A retrospective electronic chart review was conducted on all patients (pts) with resected high-risk colon cancer or metastatic colorectal cancer treated at the BC Cancer Agency with at least one cycle of single-agent capecitabine over a one year period. Dose-limiting toxicities (DLT) were defined as those requiring a dose reduction and/or delay. For each cycle, the dose, toxicities, and impact on treatment were recorded. Percent of total dose delivered was determined for adjuvant therapy based upon a total planned dose delivery of 1,250 mg/m2 for 8 cycles. Results: 124 pts were included: Mean age 68y (30–87y), 54% male, 69% adjuvant (33% stage II, 67% stage III), 31% metastatic (79% first-line), 70% with an eGFR > 60 ml/min. Only 32% of patients received a 1,250 mg/m2 treatment dose. When specified, the most common reason for starting at a reduced dose were age (37%), comorbidities (20%) and impaired PS (15%). 69% of pts experienced at least one DL toxicity, whether it was HFS (44%) or other (45%). However, the frequency of DL hand foot syndrome (HFS) was greater than all other toxicities combined, as pts often required 2 or more dose modifications for HFS. Among those treated with adjuvant intent, 22% of pts discontinued capecitabine prior to completion of 8 cycles due to toxicity. Only 23% of adjuvant pts received ≥80% of total planned dose. Conclusions: Our findings suggest that dose reductions of capecitabine are much more common in real world practice than previously reported in clinical trials. The majority of pts are started at a reduced dose. Of notable concern, when used in the curative-intent setting, 77% of patients received less than 80% of planned capecitabine adjuvant dose delivery. While the use of capecitabine monotherapy may select for an older and frailer patient population, this degree of dose modification, particularly in the adjuvant setting, is worrisome. Increased efforts to optimize toxicity management and evaluate the efficacy impact of dose-reduced capecitabine are required. No significant financial relationships to disclose.
Neighboring base effects on substitution rates in pseudogenes.
Authors: M Bulmer
Journal: Molecular Biology and Evolution (1986)

Substitution rates in pseudogenes can be used to estimate the frequencies of different types of mutation on the assumption that pseudogenes are not subject to selective constraints. These rates are used here to investigate the effect of neighboring bases on mutation rates. There is a marked increase in the frequency of transitions, though not of transversions, from the doublet CG. There are also some smaller effects of neighboring bases on the frequencies of transitions from adenine and thymine. The results are used to predict dinucleotide frequencies in a stretch of DNA subject to no selective constraints and to investigate the possibility of non-randomness in the usage of stop codons.
Hemoglobin Montreal: a new variant with an extended beta chain due to a deletion of Asp, Gly, Leu at positions 73, 74, and 75, and an insertion of Ala, Arg, Cys, Gln at the same location
Authors: D Plaseska, AJ Dimovski, JB Wilson, BB Webber, HA Hume, TH Huisman
Journal: Blood (1991)
Predicting mortality in intensive care patients with acute renal failure treated with dialysis.
Authors: C E Douma, W K Redekop, J H van der Meulen, R W van Olden, J Haeck, D G Struijk, R T Krediet
Journal: Journal of the American Society of Nephrology (1997)

Existing prognostic methods were compared in their ability to predict mortality in intensive care unit (ICU) patients on dialysis for acute renal failure (ARF). The clinical goal of this study was to determine whether these models could identify a group of patients where dialysis would provide no benefit because of a near 100% certainty of death even with dialysis treatment. This retrospective cohort study included 238 adult patients who received a first dialysis treatment for ARF in the ICU. This study examined the performance of seven general ICU mortality prediction models and four mortality prediction models developed for patients with ARF. These models were assessed for their ability to discriminate mortality form survival and for their ability to calibrate the observed mortality rate with the expected mortality rate. The observed in hospital mortality was 76% for our patient group. Areas under the receiver operating characteristic curve ranged from 0.50 to 0.78. With the Acute Physiology and Chronic Health Evaluation (APACHE) III and the Liano models, the observed mortality in the highest quintiles of risk were 97% and 98%. In conclusion, although none of the models examined in this study showed excellent discrimination between those patients who died in hospital and those who did not, some models (APACHE III, Liano) were able to identify a group of patients with a near 100% chance of mortality. This indicates that these models may have some use in supporting the decision not to initiate dialysis in a subgroup of patients.
Amelioration of Embryotoxicity by Structural Modification of the Terminal Group of Cancer Chemopreventive Retinoids&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: C C Willhite, Y F Shealy
Journal: JNCI Journal of the National Cancer Institute (1984)

An oral dose of all-trans-retinoic acid or 13-cis-retinoic acid in the pregnant [Lak:LVG(SYR)] hamster caused a dose-dependent increase in malformations in the offspring, but an equivalent dose of all-trans-N-ethyl retinamide or 13-cis-N-ethyl retinamide failed to result in embryotoxicity. The present results show that structural modification of the retinoid skeleton can produce compounds that retain cancer chemopreventive activity but that lack the teratogenic activity common to many synthetic and naturally occurring forms of vitamin A. The results indicate that in the case of the retinoids the two kinds of activity--interference with the process of carcinogenesis and interference with embryonic development--may be divorced.
Prevalence of self reported physician diagnosed asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap syndrome
Authors: Roberto de Marco, Giancarlo Pesce, Alessandro Marcon, Simone Accordini, Leonardo Antonicelli, Cristina Bombieri, Massimiliano Bugiani, Lucio Casali, Maria Grazia Panico, Pietro Pirina, Giuseppe Verlato, Isa Cerveri
Journal: European Respiratory Journal (2012)

The joint distribution of asthma and COPD has not been well described in the general population.  We studied the prevalence of self-reported physician-diagnoses of asthma, COPD and asthma/COPD overlap syndrome in the general population.  In the Gene-Environment Interactions in Respiratory Diseases study, a postal screening questionnaire, which included questions on physician diagnosed asthma and COPD and respiratory symptoms, was administered in 4 Italian cities to random samples of subjects aged 20-44 (n=9739), 45-64 (n=3480) and 65-84 years (n=1975).  The prevalence of diagnosed asthma decreased with age while that of COPD with or without asthma showed an opposite pattern (p  Subjects with both asthma and COPD had the highest prevalence of respiratory symptoms (p  Subjects with both the diagnoses of asthma and COPD represent a relevant clinical population with more severe and frequent exacerbations.
Statistical properties of bootstrap estimation of phylogenetic variability from nucleotide sequences. I. Four taxa with a molecular clock.
Authors: A Zharkikh, W H Li
Journal: Molecular Biology and Evolution (1992)

The statistical properties of sample estimation and bootstrap estimation of phylogenetic variability from a sample of nucleotide sequences are studied by using model trees of three taxa with an outgroup and by assuming a constant rate of nucleotide substitution. The maximum-parsimony method of tree reconstruction is used. An analytic formula is derived for estimating the sequence length that is required if P, the probability of obtaining the true tree from the sampled sequences, is to be equal to or higher than a given value. Bootstrap estimation is formulated as a two-step sampling procedure: (1) sampling of sequences from the evolutionary process and (2) resampling of the original sequence sample. The probability that a bootstrap resampling of an original sequence sample will support the true tree is found to depend on the model tree, the sequence length, and the probability that a randomly chosen nucleotide site is an informative site. When a trifurcating tree is used as the model tree, the probability that one of the three bifurcating trees will appear in > or = 95% of the bootstrap replicates is < 5%, even if the number of bootstrap replicates is only 50; therefore, the probability of accepting an erroneous tree as the true tree is < 5% if that tree appears in > or = 95% of the bootstrap replicates and if more than 50 bootstrap replications are conducted. However, if a particular bifurcating tree is observed in, say, < 75% of the bootstrap replicates, then it cannot be claimed to be better than the trifurcating tree even if > or = 1,000 bootstrap replications are conducted. When a bifurcating tree is used as the model tree, the bootstrap approach tends to overestimate P when the sequences are very short, but it tends to underestimate that probability when the sequences are long. Moreover, simulation results show that, if a tree is accepted as the true tree only if it has appeared in > or = 95% of the bootstrap replicates, then the probability of failing to accept any bifurcating tree can be as large as 58% even when P = 95%, i.e., even when 95% of the samples from the evolutionary process will support the true tree. Thus, if the rate-constancy assumption holds, bootstrapping is a conservative approach for estimating the reliability of an inferred phylogeny for four taxa.
Postoperative radiotherapy for prostate cancer: Sooner or later?
Authors: S. Igdem, M. U. Abacioglu, G. Alço, R. Ibrahimov, A. Kefeli, I. Çetin, S. Turkan, S. Okkan
Journal: Journal of Clinical Oncology (2009)

e16157 Background: To report our experience with adjuvant or salvage radiotherapy for prostate cancer and to assess the tolerance of the patients. Methods: The charts of 139 men who received postoperative radiotherapy (RT) after radical prostatectomy (RP) between 1997–2007 in two institutions were retrospectively analyzed. Thirty-seven percent received adjuvant RT and 63% salvage RT. The median age was 65 years (range: 43–80). Pathologic Gleason score was 2–6 in 24%, 7 in 56%, and 8–10 in 20%. Seminal vesicle involvement was reported in 34%, positive surgical margins in 72%, lymph node involvement in 7%, capsular perforation in 61%, and perineural invasion in 73% of the patients. The median PSA level before RT was 0.29ng/ml (range: 0–19ng/mL). Median time from RP to RT was 3 months (range, 1–12 months) in the adjuvant setting, and 27 months (range, 2–96 months) in the salvage setting. Nineteen percent received radiation to the pelvis, 81% to the prostate bed only. The median dose to the prostatic bed was 66.6Gy (range: 60–76Gy). Before, during or after RT 49% received androgen deprivation for a median of 6 months (range, 3–48 months). Biochemical failure is defined as a post-RT PSA level &gt;0.2ng/mL. Results: The median follow up time was 41 months (range, 12–133 months). At 4 years, for the entire cohort biochemical control, metastasis free survival, and overall survival was 68%, 92%, and 94%, respectively. Although there was a significant difference in favor of the adjuvantly treated group for biochemical control (81% vs 60%, p = 0.03) in univariate analysis, multivariate analysis demonstrated that higher preoperative PSA level (p = 0.02), and lymph node involvement (p = 0.02) predicted for a worse PSA outcome. No grade 3 acute gastrointestinal (GI) or genitourinary (GU) toxicity was reported during the treatment. At 4 years, 4% of patients had Grade 2 late GI toxicity, 0.7% had grade 3 late GI, and 0.7% brade 4 late GI toxicity, while 16% of patients reported late grade 2 GU, and 4% had late grade 3 GU toxicity. Conclusions: Our results suggest that adjuvant RT may offer a better biochemical outcome in patients who underwent radical prostatectomy for prostate cancer. Overall, the number of high grade toxicities for postoperative RT was low. Therefore it can safely be used in appropriate setting. No significant financial relationships to disclose.
Phase I study of immunization with dendritic cells (DC) modified with recombinant fowlpox encoding carcinoembryonic antigen (CEA) and the triad of costimulatory molecules CD54, CD58, and CD80 (rF-CEA(6D)-TRICOM) in patients with advanced malignancies
Authors: M. Morse, T. Clay, A. Hobeika, T. Osada, D. Panicali, H. K. Lyerly
Journal: Journal of Clinical Oncology (2004)

2508 Background: We hypothesize that the activity of vaccines based on DC loaded with tumor antigens will be enhanced by modifications that increase antigen expression and costimulatory activity of the DC. Methods: In an ongoing phase I study, we are administering 1, 2, or 3 cycles of 4 triweekly subcutaneous / intradermal injections of ex vivo generated DC (5 x 10E6 cells) modified with the recombinant fowlpox vector rF-CEA(6D)-TRICOM (2.5 x 10E7 pfu/5 x 10E7 DC). Results: Thus far, 14 patients have been enrolled into the first 2 cohorts. There were no grade 3/4 toxicities directly referable to the immunizations. One patient had a decrease in the CEA level from 46 to 6.8 and a minor regression in supraclavicular adenopathy that occurred several months after completion of the immunizations. Three other patients were stable through at least 1 cycle of immunization (3 months). Direct analysis of T cells in peripheral blood using the ELISpot assay demonstrated an increase in the frequency of T cells specific for the CEA-expressing vector in 10 of the 12 patients completing participation (range 10 to 541 CEA-specific cells/100,000 peripheral blood mononuclear cells (PBMC).) A greater CEA-specific response was observed for patients with either a minor response or stable disease following at least 1 cycle of therapy compared with those who progressed (mean of 241 vs 50 CEA-specific cells/100,000 PBMC, P=0.03). Cytokine flow cytometry demonstrated that the CEA-specific immune response occurred amongst both CD4 and CD8+ T cells in all responders. Changes in the frequency of CD4+CD25+ regulatory T cells were observed and, in some patients, were inversely correlated with the frequency of CEA-specific CD4+ T cells suggesting that regulatory mechanisms might impact the greatest magnitude of CEA-specific T cells that can be achieved. Conclusions: This immunization strategy is safe and feasible and activates potent CEA-specific immune responses. This study will continue into the third cohort. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Therion Biologics Corp.
Potentiation of proteasome inhibitor-induced apoptosis in glioma cells by histone deacetylase inhibitors
Authors: B. Friday, C. Yu, L. Yang, D. Wigle, J. Sarkaria
Journal: Journal of Clinical Oncology (2007)

2038 The effects of combining histone deacetylase (HDAC) inhibitors and proteasome inhibitors were evaluated in both established glioblastoma multiforme (GBM) cell lines and short-term cultures derived from the Mayo Clinic xenograft GBM panel. Co-exposure of LBH589 (LBH) and botezomib (btzmb) results in a striking induction of apoptosis, at minimally toxic doses of either drug alone, in established U251, U87, and D37 GBM cell lines, as well as in GBM8 (G-8), GBM10 (G-10), GBM12 (G-12), GBM14 (G-14), and GBM56 (G-56) cells, which have been developed from the Mayo xenograft GBM panel and maintained in short-term cultures. Synergism of apoptosis induction was also observed in U251 cells when co-exposing other HDAC inhibitors, including LAQ824 (LAQ) and trichostatin A (TSA), with another proteasome inhibitor MG132, demonstarting a class effect. In U251 cells, btzmb alone or in combination with LBH decreased Raf-1 levels and inactivated Akt and Erk. Either LBH589 or bortezomib alone increased expression of the cell cycle regulators p21 and p27. Additionally, the combination, but not the individual agents, markedly increased JNK activation. In addition, cell death after exposure to LBH589 and bortezomib is associated with cytochrome c release, Bax translocation, as well as caspase and PARP cleavage. Bax translocation may contribute to the synergistic cytotoxicity of the combination of LBH and btzmb in glioma cells since Bax translocation to mitochondria is known to precede cytochrome c release and apoptosis, but other pathways are likely to be involved. This combination regimen warrants further preclinical and possible clinical study for glioma patients. No significant financial relationships to disclose.
Utilizing a “navigation app” to ensure quality and consistency of oncology patient navigation.
Authors: Heather Sheaffer
Journal: Journal of Clinical Oncology (2013)

251 Background: Measuring the impact of the patient navigator has presented an on-going challenge since the inception of patient navigation in 1990. The Oncology Navigation team initially relied upon a spreadsheet to record data later utilized to evaluate the quality of the program however the spreadsheet did not meet the needs of the navigators nor of those who attempted to make sense of the voluminous data collected. This abstract offers an overview of the creation and implementation of a Navigation App to record the navigation workflow-ensuring quality and consistency in practice. Methods: The Navigation App is a web-based platform serving as the framework into which navigation data is entered. The customized version allows the collection of data specific to the metrics of interest to navigation including: care coordination, triage, reinforcement of the care plan and appointment scheduling. The App was designed as a means of evaluating the quality of the navigation process but also serves as a useful tool in organizing the navigators’ daily workflow. Results: The creation and implementation of a Navigation App has illuminated the complexity of the role of the navigator by recording both quantitative and qualitative data. The App allows the navigators to collect “real-time” data detailing their daily workflow with patients, families and providers. The navigators were quickly able master the App and significantly reduce the time needed to record data from hours to minutes each month. Entering data into the App concurrently also allows for instantaneous evaluation of productivity and quality. Finally, the App has proved to be a valuable tool for navigators in organizing their daily workflow and in prioritizing patient and provider needs. Conclusions: A web-based Navigation App can serve as an invaluable tool in driving quality patient navigation. The App not only serves as a means of recording data but also as an organizational tool to maximize productivity, quality and consistency of navigation. Utilizing a web-based application as opposed to a spreadsheet allows both navigators and administrators to track workflows in “real time” to ensure the highest quality of service to cancer patients, families and providers.
Bilateral Pneumothoraces after Unilateral Lung Biopsy. A Case of “Buffalo Chest”?
Authors: Adam Jacobi, Corey Eber, Andrew Weinberger, Saul N. Friedman
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

An 81-year-old man with a productive cough was found to have multiple bilateral pulmonary nodules and was referred for biopsy. Under computed tomography guidance, fine-needle aspiration of a right lower lobe nodule led to a diagnosis of lung adenocarcinoma (Figure 1). A small pneumothorax developed on the right and, despite the fact that the left lung and mediastinum were not manipulated during the procedure, extended into the left hemithorax. Both pneumothoraces resolved without intervention. “Buffalo chest” is a term derived from the animal’s peculiar anatomy in which there is only one contiguous pleural space containing both lungs. Previous reports in the literature (approximately 10–15 cases) are almost universally in patients with prior thoracic surgery causing disruption of the mediastinal barrier (i.e., esophagectomy [1], heart–lung transplant [2], pneumonectomy), with only a few existing “congenital pleuro-pleural communication” cases (3). Bilateral pneumothoraces have also been described after unilateral procedures in patients prone to spontaneous pneumothoraces (1, 4) and in patients with sarcoma metastases receiving chemotherapy (5). This patient had no prior surgical history or emphysematous/cystic lung disease, raising the possibility of a congenital condition, despite a seemingly intact mediastinum on computed tomography. Disruption of the mediastinal pleura from lung metastases is another etiology to consider, as has been previously hypothesized (5). n