tbuckley/cabot-search huggingface dataset:
Harvesting bone marrow in an outpatient setting using newer anesthetic agents.
Authors: A C Thorne, M Stewart, S C Gulati
Journal: Journal of Clinical Oncology (1993)

To evaluate the results of outpatient bone marrow harvest (BMH).Seventy-two adult patients with various malignancies had 79 BMH procedures performed for future autologous bone marrow transplantation (BMT) in our institution's outpatient surgical facility. All patients were evaluated and educated before the procedure. Newer anesthetic agents specifically developed to have shorter half-lives, more rapid recovery from general anesthesia, and fewer unpleasant side effects were chosen. Propofol was used for induction of anesthesia in 76 patients, the other three were induced with sodium pentothal. The blood volume removed was replaced by colloid (6% hydroxyethyl starch). Also, a new parenteral nonnarcotic pain medication, ketoroloc, was used during the last part of general anesthesia to help with expected postoperative pain in 76 patients.BMH took 111 +/- 24 minutes and patients were in postanesthesia care unit (PACU) for 220 +/- 72 minutes before being sent home with a companion and Tylenol with codeine (acetaminophen with codeine; McNeil Pharmaceutical, Spring House, PA). PACU complications were minor and included transient mild dizziness (7.6%), vomiting (3.8%), and fever (2.6%). No life-threatening complication was observed. Only one patient was hospitalized for observation (fever) and then sent home. Seventy-five patients (94.9%) were contacted at home by the hospital nursing staff the day following the procedure. Five (6.7%) complained of nausea or vomiting, and four (5.3%) developed fever at home (temperature, 37.2 to 38.3 degrees C). Only 36% of patients actually took oral narcotic pain medication at home.Autologous BMH (AuBMH) is a safe outpatient procedure with minimal side effects when newer anesthetic agents are used.
Preclinical evidence of ET-743 as a potential chemotherapy option for the treatment of biliary carcinoma.
Authors: Francesco Leone, Caterina Peraldo-Neia, Giuliana Cavalloni, Marco Soster, Loretta Gammaitoni, Serena MarchiÃƒÂ², Massimo Aglietta
Journal: Journal of Clinical Oncology (2013)

193 Background: The standard chemotherapy for unresectablebiliary tract carcinoma (BTC) is based on gemcitabine and platinum compounds. However, these combinations have not been shown to be effective in improving long-term survival. Thus, there is a real need to find new strategies that would impact in a significant way on clinical outcome. Ecteinascidin-743 (ET-743), a compound isolated from the marine tunicate Ecteinascidia turbinata. ET-743, is approved for the treatment of ovarian cancer and soft tissue sarcoma. Phase II and III clinical trials are ongoing for the treatment of different solid tumors. No preclinical data are available about the efficacy of ET-743 in BTC. In a phase I study, one patient received ET-743 plus capecitabine and experienced a long lasting complete metabolic response. Here, we investigated the antitumor activity of ET-743 in preclinical BTC models. Methods: Four BTC cell lines TFK1, EGI-1, HuH28 and TGBC1 were used to evaluate the effect of ET-743 on proliferation, cell cycle, apoptosis and on the activation of DNA damage proteins. The effect on proliferation was also investigated on a primary cell culture of a gallbladder carcinoma (GBC) resistant to gemcitabine and oxaliplatin. On the same cells, the inhibition of VEGF secretion mediated by ET-743 was analyzed by ELISA. The anti-tumor activity of ET-743 was tested on EGI-1 xenografts in NOD/SCID mice. Results: In vitro, ET-743 is able to markedly reduce cell proliferation of BTC cell lines through cell cycle blockage on G0/G1 phase and to inhibit the growth of primary cell culture derived from GBC patient. Moreover, ET-743 promotes apoptosis by caspase 3 activation, activates proteins involved in DNA damage and reduces VEGF secretion. In the in vivo model, ET-743 is able to slow tumor growth in BTC xenograft. The mechanism of anti-tumor activity involves DNA damage, the induction of hypoxia transcription factor-1, and angiogenesis inhibition. ET-743 has no significant effect on apoptosis in vivo. Conclusions: These data suggest that ET-743 could represent an alternative chemotherapy for BTC treatment and encourage the development of clinical trials of ET-743 in BTC patients.
Sequential high-dose cytosine arabinoside-asparaginase treatment in advanced childhood leukemia.
Authors: R J Wells, J Feusner, R Devney, W G Woods, A J Provisor, M S Cairo, L F Odom, J Nachman, G R Jones, L J Ettinger
Journal: Journal of Clinical Oncology (1985)

Sequential high-dose cytosine arabinoside (ara-C) and asparaginase were given to 41 children age six months to 21 years of age with advanced leukemia. Ten of 22 patients with acute lymphocytic leukemia (ALL) and eight of 19 patients with acute nonlymphocytic leukemia (ANLL) obtained complete remissions. The most significant toxicity seen was infection in 22 patients. In addition, patients given intrathecal chemotherapy within 24 hours of ara-C developed neurologic toxicity. The high response rate seen in these patients with advanced leukemia indicates that a trial of this regimen is warranted in children with less advanced ALL and ANLL.
Immunohistochemical staining of the Excision Repair Cross-Complementing 1 (ERCC1) protein as predictor for benefit of adjuvant chemotherapy (CT) in the International Lung Cancer Trial (IALT)
Authors: J. Soria, V. Haddad, K. A. Olaussen, P. Fouret, A. Dunant, M. Filipits, H. H. Popper, F. André, T. Le Chevalier, E. Brambilla
Journal: Journal of Clinical Oncology (2006)

7010 Background: Adjuvant cisplatin-based chemotherapy improves survival in patients with completely resected non-small-cell lung cancer, but no clinical or biological predictor of the benefit of CT has yet been validated in large trials. ERCC1 is a highly conserved excision nuclease within the nucleotide excision repair (NER) pathway and is essential for efficient repair of DNA-adducts induced from alkylating agents. Methods: Using a standard protocol of immunohistochemistry, we evaluated ERCC1 expression in 783 resected tumor tissues from patients enrolled in the IALT. For each case, a semi-quantitative histology score (H-score) was calculated on the basis of both the percentage of positive tumor nuclei and staining intensity. The median value of H-scores was a priori chosen as the cut-off point to classify ERCC1 positive and negative tumors. Overall survival was analyzed with a Cox model adjusted on clinical and pathological factors. Results: After immunostaining, 761 out of 783 cases (97%) were of sufficient quality for analysis. For 335 patients (44%), ERCC1 status was positive (H-score exceeding 1.0, i.e. tumors with a staining intensity score of 2 and 50% or more positive nuclei or a staining intensity score of 3 and 10% or more positive nuclei). The benefit of cisplatin-based adjuvant CT was correlated with the ERCC1 status (test for interaction, P&lt;0.009). Patients with ERCC1-negative tumors randomized to CT had significantly prolonged survival compared with patients with ERCC1-negative tumors randomized to observation (adjusted hazard ratio for death, 0.67; 95% confidence interval [0.51–0.89], P&lt;0.006). There was no survival difference with CT among ERCC1 positive patients (adjusted hazard ratio for death, 1.18; [0.87–1.61], P=0.29). When analyzing only patients randomized to observation, the subgroup with ERCC1 positive tumors had a better survival compared to those with ERCC1 negative tumors (0.65; [0.48–0.89], P&lt;0.008). Conclusions: Patients with completely resected NSCLC and ERCC1-negative tumors derive a substantial benefit from adjuvant cisplatin-based CT. Unrestricted grants: Eli-Lilly, PHRC, Cancéropôle Rhône-Alpes, Austrian Science Fund No significant financial relationships to disclose.
&lt;italic&gt;Brief Communication:&lt;/italic&gt; Mouse Mammary Tumor Virus Polypeptide Precursors in Intracytoplasmic A Particles
Authors: G H Smith, B K Lee
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Brief Communication: Mouse Mammary Tumor Virus Polypeptide Precursors in Intracytoplasmic A Particles Get access Gilbert H. Smith, Gilbert H. Smith Search for other works by this author on: Oxford Academic PubMed Google Scholar Barbara K. Lee Barbara K. Lee Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 55, Issue 2, August 1975, Pages 493–496, https://doi.org/10.1093/jnci/55.2.493 Published: 01 August 1975 Article history Received: 19 February 1975 Accepted: 15 April 1975 Published: 01 August 1975
EpCAM-negative cancer–associated circulating cells (CACS) in blood samples of women with triple-negative breast cancer (TNBC).
Authors: M. B. Lustberg, P. Balasubramanian, B. Miller, A. Garcia Villa, S. Carothers, B. Michael, E. Mrozek, B. Ramaswamy, R. M. Layman, R. Wesolowski, C. L. Shapiro, J. J. Chalmers
Journal: Journal of Clinical Oncology (2011)

e11559 Background: Breast circulating tumor cells (CTCs) are commonly isolated by positive selection enrichment targeting the epithelial cell adhesion activating molecule, EpCAM. The accepted definition of CTCs is cells that have: 1) nuclei, 2) cytokeratin, 3) EpCAM and that these cell are negative for the pan-hematopoeitic marker CD45. Recent data suggests that other rare circulating cells (CACs) are present in the blood of metastatic cancer patients including CD45+ cytokeratin+ cells (Toner, 2010). It is hypothesized that these cells are tumor cells of a different phenotype or that are interacting with or ingested by hematopoeitic cells. We aimed to evaluate CACS in TNBC using a negative depletion technology. Methods: Ten women with metastatic triple negative breast cancer were enrolled. Blood was processed using previously described immunomagnetic negative depletion (Jatana et al. 2010; Yang et al. 2009). Multiparameter, flow cytometry analysis was conducted prior to, and after depletion of CD45 cells. Multistep, sequential labeling was performed to first label and fix cell surface markers. Subsequently, cells were fixed and permeablized for cytokeratins. Immunocytochemical (ICC) staining for nucleus, cytokeratin (8, 18,19) and CD45 was completed and spectral data using Nuance microscope was utilized. Results: No cytokeratin positive cells were present in blood samples of healthy volunteers or in buffy coat. Samples from healthy volunteers (n=7) and buffy coats with and without spiked MCF-7 cells were run as controls. All metastatic patients had multiple subpopulations of interest, prior to, and after negative depletion enrichment, including a) CD45-, EpCAM+, cytokeratin+, b) CD45-, EpCAM-, cytokeratin+, c) CD45-, EpCAM-, CK-, and d) CD45+, EpCAM+, CK+, CD13+. We also observed similar subpopulations using ICC with spectral analysis using a Nuance camera and software. Conclusions: Several distinct populations of rare circulating cells are present in blood samples of patients with TNBC. These include cytokeratin positive cells that were CD45+ (CACS) and CD45- (CTCs). The importance of these rare circulating cells will need to be further evaluated in future studies.
Molecular phylogeny of the symbiotic actinomycetes of the genus Frankia matches host-plant infection processes.
Authors: B Cournoyer, M Gouy, P Normand
Journal: Molecular Biology and Evolution (1993)

Nucleotide sequences of approximately 213 bp of the nif H-D intergene and the beginning of nifD were determined for symbiotic Frankia isolates from the major host-infectivity groups. This region of the nif operon is variable enough to classify most infective Frankia strains at the species level. Phylogenetic inferences from these sequences are in agreement with the 16S rRNA-derived phylogeny of the genus and, thus, are in favor of an intrageneric evolution of nif genes by orthology. Phylogenetic lineages derived from combined nifH-D intergene and partial nifD and 16S rRNA sequences are supported for at least 93% of bootstrap replicates and are useful for investigating evolutionary relationships of the genus and symbiotic properties of this microorganism. The genus Frankia is divided into two major phylogenetic clusters that match with the separation of species according to the mechanism of infection of actinorhizal plants. One cluster groups species strictly adapted to the mechanism of root hair infection (RHI), and the other groups species adapted to the mechanism of direct intercellular penetration. In the RHI cluster, the species infective on Casuarina plants appears to have emerged from strains infective on Alnus. The concordance between the symbiotic properties and the molecular phylogeny of Frankia strains indicates a major role for the host plant in the evolution and speciation of the genus Frankia.
Performance of the Cytoanalyzer in Recent Clinical Trials
Authors: C C SPENCER, R C BOSTROM
Journal: JNCI Journal of the National Cancer Institute (1962)

The results of two clinical trials of the Cytoanalyzer are summarized. The first, conducted in 1958–59, included 1,184 smears, of which 21 were positive. Four hundred twenty-five (36.6%) of the negative smears received instrument scores lower than the lowest-scoring positive smear. In the second clinical trial, which took place in 1959–60, 58 of the 11,136 smears scanned by the Cytoanalyzer were positive. At the level of screening achieved in the first clinical trial (36.6%), a false-negative rate of 10.3 percent was incurred; that is, 6 of the 58 positive smears received scores within the selected negative range. This screening performance is considered inadequate for practical application of the instrument. An investigation of the mechanisms for screening revealed a direct relationship between the relative number of leukocytes in the smears and the instrument score achieved by the smears. This, in turn, was the result of nuclear aggregations, which increased in size and frequency with the proportion of leukocytes present and were responsible for most of the entries registered in the “abnormal” zone categories. Typical examples of normal and abnormal nuclei consistently failed to produce entries in the “normal” and “abnormal” zone categories, a result of the manner in which zone designations had been made. The inadequacies of smear-preparation techniques used in the clinical trials and the necessity of improving them are discussed.
Knowledge gaps about Tamiflu and Relenza for pandemic flu are blamed on research failure
Authors: Nigel Hawkes
Journal: BMJ (2015)

A failure to carry out research during the 2009 flu pandemic has left the world unprepared for another one, with huge gaps in the knowledge base that should by now have been filled, says a report from the Academy of Medical Sciences and the Wellcome Trust.1

Research into infectious diseases is “woeful,” said Jeremy Farrar, director of the trust, at a briefing to introduce the report at the Science Media Centre in London. No vaccines were available to prevent severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), he said, and it had taken six to nine months to set up trials for an Ebola vaccine. Furthermore, the numbers involved in trials during the 2009 H1N1 flu pandemic had been “close to zero.”

As a result, it is not known how well antiviral drugs such as oseltamivir (Tamiflu) and zanamivir (Relenza) …
Tubular resistance to furosemide contributes to the attenuated diuretic response in nephrotic rats.
Authors: K A Kirchner, J R Voelker, D C Brater
Journal: Journal of the American Society of Nephrology (1992)

A blunted response to loop diuretics frequently occurs in nephrotic syndrome (NS). Observations that nephrotic humans have reduced sodium excretion at normal rates of diuretic excretion have suggested that tubular resistance to the drug may contribute to diuretic resistance. To determine if tubular resistance to furosemide exists in NS, late proximal and early distal tubular micropuncture was performed in rats with puromycin aminonucleoside-induced NS and in control rats after an i.v. bolus dose of furosemide of 1 mg/kg body wt. Absolute and fractional urinary sodium excretions were less (P less than 0.05) in NS rats than in control rats after furosemide. Inulin clearance and total urinary furosemide excretion, however, were not different between groups. Thus, similar to reports in humans, the urinary sodium-to-furosemide excretion ratio was less (P less than 0.05) in NS than in control rats. Single-nephron GFR and chloride delivery to late proximal sites were not different between groups after furosemide. In contrast, absolute and fractional chloride deliveries to early distal sites were less (P less than 0.05) in NS rats after furosemide. Calculated loop chloride reabsorption after furosemide was greater (P less than 0.05) in NS than in control rats when expressed either as percentage of filtered load (39.4 +/- 3.1 versus 28.2 +/- 2.0%) or delivered load (67.9 +/- 4.7 versus 48.3 +/- 3.0%). Loop fluid reabsorption was not different between groups. Thus, loop chloride reabsorption is inhibited to a lesser extent by i.v. furosemide in NS than in normal rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Quality improvement in fellowship training programs: The pilot quality oncology practice initiative (QOPI) project
Authors: N. J. Farrell, K. McNiff, K. McCaffrey, L. Lyckholm
Journal: Journal of Clinical Oncology (2008)

17523 Background: Oncology fellowship programs train physicians in many core competency areas, one of which is practice-based learning and improvement. In spring 2007, Virginia Commonwealth University was among the first eight fellowship programs to participate in ASCO's Quality Oncology Practice Initiative (QOPI). QOPI is a practice-based quality improvement (QI) program that provides a mechanism for self-examination and improvement. Fellowship programs participating in QOPI receive feedback comparing their performance with more than 100 U.S. community and academic practices. Methods: Six charts per fellow were selected from the fellows’ clinic according to QOPI methodology. Peers abstracted data using QOPI measures, and the information was included in the nationwide QOPI database from which a comparative report was provided. Results were discussed in a fellowship didactic. ASCO practice guidelines were reviewed and plans were developed to improve documentation. Results: The abstraction process alone resulted in meaningful discussion regarding cancer quality measures. The fellows’ clinic performed above average for almost all quality indicators both within the core quality measures as well as the breast cancer module. A few areas including documentation of the intent of treatment, following erythropoetin guidelines and the use of aprepitant were below average. In a brief survey, all fellows found QOPI to be helpful in learning QI, and considered it useful for current and future practice. Plans were made to participate in future QOPI data collections. Conclusions: QOPI provides a tool for practicing oncologists to assess the quality of care they provide, and fulfills many of the core competencies of fellow education. Providing fellows the opportunity to participate in QOPI establishes a pattern of quality improvement that may continue into future practice. It teaches fellows about peer review, and encourages dialogue about quality indicators in patient care. The next step will be to see if the educational intervention impacted the quality indicators on the fall 2007 QOPI data collection. No significant financial relationships to disclose.
Molecular analysis of duplicated esterase genes in Drosophila melanogaster.
Authors: C Collet, K M Nielsen, R J Russell, M Karl, J G Oakeshott, R C Richmond
Journal: Molecular Biology and Evolution (1990)

Genomic clones containing sequences homologous to an esterase 6 (Est-6) cDNA clone were isolated from a library of Drosophila melanogaster DNA. Comparison of the genomic and cDNA sequences revealed that the Est-6 gene comprises two exons, one of 1,387 bp and one of 248 bp, separated by a short intron of 51 bp. Further sequencing revealed the presence of a tandem duplication of the Est-6 gene (denoted Est-P) which also has an exon of 1,387 bp and an exon of 248 bp, separated by a short intron of 56 bp. The two genes show similarities of 64% and 60% at the DNA and protein levels, respectively. The coding regions of the genes are 197 bases apart, and presumptive 5' regulatory sequences of Est-P overlap at least the 3' noncoding region of Est-6. Transcripts homologous to Est-P were detected in late larvae and adults of each sex, whereas Est-6 transcripts are present in all life stages but are predominant in adult males. This suggests different physiological functions for the products of the two genes. Southern and Northern blot hybridization analyses of the 20-kb region surrounding the Est-6/Est-P duplication failed to detect any other duplicated esterase genes, although this region is actively transcribed.
Abstract 16646: The Left Atrium Emptying Fraction Improves Diagnosis of Paroxysmal Atrial Fibrillation After Cryptogenic Ischemic Stroke
Authors: Tor Biering-Sorensen, Louisa M Christensen, Derk W Krieger, Rasmus Mogelvang, Jan Skov, Soren Hojberg, Nis Host, Finn M Karlsen, Hanne Christensen
Journal: Circulation (2013)

Background: In 25% of patients with ischemic stroke, no etiologic factor is identified, so-called cryptogenic strokes (CS). Asymptomatic paroxysmal atrial fibrillation (PAF) is often suspected to b...
Sequences and evolutionary analysis of mouse 5S rDNAs.
Authors: H Suzuki, K Moriwaki, S Sakurai
Journal: Molecular Biology and Evolution (1994)

We selectively amplified the spacer regions of genes for mouse 5S ribosomal RNA (rRNA), which are tandemly repeated, by the PCR method, using primers specific to the two ends of the coding region for 5S rRNA. Fragments of approximately 1.6 kb were amplified from DNA from the BALB/cCrSlc mouse (Mus musculus domesticus), the SM/J mouse (M. m. domesticus), the MOA mouse (M. m. musculus) and the SEG mouse (M. spretus). These fragments were cloned into an appropriate plasmid vector, and two clones representative of each of the four strains were sequenced. The sequences were GC rich (> 60%) and contained a high proportion of very simple repetitive motifs, such as (TG)n and (ATCC)n, which accounted for the intra- and intergenomic length heterogeneity. Excluding such polymorphic regions and neglecting small insertions or deletions, we estimated the sequence divergence between clones. Sequence divergence within a genome averaged 0.26%, and the divergence between individuals of the same subspecies, between subspecies, and between species was 0.44%, 0.62%, and 1.73%, respectively. The results indicate that the spacer region evolved rapidly but with a reduction in heterogeneity within each genome, as a result of certain, as yet unidentified, homogenization mechanisms. The results further suggest that the spacer regions of genes for 5S rRNA may provide good indicators for phylogenetic analysis of closely related species.