tbuckley/cabot-search huggingface dataset:
Cigarette smoking inhibits LTA4H aminopeptidase activity and contributes to chronic neutrophilic airway inflammation and COPD
Authors: James Wells, James Blalock, Philip O'Reilly
Journal: European Respiratory Journal (2011)

Proline-glycine-proline (PGP) acts as a potent neutrophil chemokine and marker for COPD and substrate for the triaminopeptidase (TAP) site of LTA4H, a bifunctional enzyme made by neutrophils. Normally, LTA4H degrades PGP and leads to resolution of inflammation but cigarette smoke selectively inhibits TAP activity, preventing PGP breakdown and promoting neutrophil accumulation in vitro and in animal models. We hypothesized that neutrophils would be elevated and TAP activity would be diminished in serum and induced sputum (IS) from smokers (CS) compared to non-smokers (NS).

IS was collected, immunoprecipitated (IP), Western blotted (WB), and underwent separate ELISAs specific for LTA4H and myeloperoxidase (MPO). Serum samples were collected and treated with bestatin, an inhibitor of TAP activity, or normal saline. TAP activity was determined by PGP breakdown, as measured by mass spectrometry.

Smoking causes increased airway neutrophils as detected by MPO levels. Sputum LTA4H amounts are higher in CS than NS, as measured by WB band intensity and ELISA, even though the TAP activity is similar based on PGP degradation. Consequently, the IP-WB and ELISA along with the TAP assay demonstrate the profound inhibitory effect and impact of cigarette smoke on TAP activity in the airways of CS. The addition of bestatin to sera suggests that TAP activity is systemically inhibited by cigarette smoke.

Smoking inactivates TAP activity in the airways of humans. The effects of smoking seem to be systemic since TAP activity appears to be inhibited in sera from CS as compared to NS. These findings may provide a new link between smoking, chronic neutrophilic inflammation, and COPD.
Phase II trial with carboplatin/gemcitabine (Cb/G) induction chemotherapy (CT) followed by radiotherapy concomitantly with paclitaxel/gemcitabine (P/G) in stage III non small cell lung cancer (NSCLC): Preliminary report
Authors: V. Hirsh, M. Duclos, P. Del Vecchio, L. M. Ofiara, J. P. Ayoub, S. Faria, D. Charpentier, L. Portelance, L. Souhami, D. Soulieres
Journal: Journal of Clinical Oncology (2005)

7122 Background: The optimal combination of concomitant thoracic radiotherapy (TRT) and CT in stage III unresectable NSCLC remains unclear. The role of induction CT with Cb/G, regimen less toxic than Cisplatin/G, has not been studied in stage III NSCLC. Methods: Forty-two patients (pts), 41 evaluable, entered this trial between January 2003 and November 2004, 27 males, 14 females, median age 60 (37–70), 19 pts with ECOG PS 0, 22 pts with PS 1, 22 pts with stage III A (N2), and 19 pts with stage III B (N2, N3). They received Cb AUC 5 i.v. on day 1 and G 1000 mg/m2 i.v. on days 1 + 8 every three weeks x 2 cycles, followed on day 50 by TRT, 60 Gy over 6 weeks, concomitantly with P 50 mg/m2 i.v. and G 100 mg/m2 i.v. on days 1 + 8 every three weeks x 2 cycles. Results: Of first 38 evaluable pts, after induction chemotherapy, partial response (PR) was 74% (28 pts), stable disease (SD) 24% (9 pts), and 2% (1 pt) had progressive disease (PD). After TRT and P/G, 21% (8 pts) had CR, 74% (28 pts) PR, and 5% (2 pts) PD. Thirty pts are still alive, 13 pts surpassed one year. Toxicity of induction CT was minimal. During TRT + CT, grade 3 neutropenia, thrombocytopenia, and anemia occurred in 8 pts, 3 pts, and 3 pts respectively with grade 4 neutropenia and thrombocytopenia in one pt each. Nine pts received red cell transfusions, and one pt had platelet transfusion. Three pts had grade 3 esophagitis, two pts grade 3 infections, and one pt grade 3 dermatitis and elevation of liver enzymes. Conclusion: This regimen is effective and well tolerated and appears to be an excellent choice for stage III NSCLC. Sponsored by Eli Lilly Canada. No significant financial relationships to disclose.
Docetaxel and capecitabine as first-line chemotherapy in patients with advanced breast cancer
Authors: C. Gennatas, V. Michalaki, J. Psychogios, S. Gennatas, A. Kondi-Paphiti, E. Karvounis, E. Kairi
Journal: Journal of Clinical Oncology (2006)

10734 Background: Capecitabine (C) and Docetaxel (D) have demonstrated synergy in both preclinical and clinical studies in metastatic breast cancer (MBC). The aim of the study was to evaluate the activity and tolerability of the combination of CD as a first -line therapy for patients with advanced breast cancer. Methods: Thirty- five patients have been enrolled in the study. Median age was 54 years (range 35–73). ECOG PS was of 0–2 (PS 0: 6 patients, PS 1: 5 patients, PS 2: 14 patients), All patients were Her-2 neu negative. Patients received Docetaxel 75 mg/m 2 on day 1, with routine pre and post-medication with steroids, and Capecitabine 950 mg/m 2 p.o. bid on days 1–14, every 3 weeks until disease progression or unacceptable toxicity. Results: A total of 233 cycles were given with a median of 7 (2–12). Of the 35 evaluable patients, 17 patients (48%) achieved partial response (PR) and 6 patients (17%) attained stable disease (SD). The median duration of response was 12 weeks and the median duration of SD was 20 weeks. The median time to progression (TTP) was 28 weeks. The median overall survival was 90 weeks. All patients were evaluable for toxicity. Toxicity was mainly hematological with G3 or 4 neutropenia in 7 patients (20%). Febrile neutropenia was not encountered. There was not significant GI toxicity. Conclusions: Combination chemotherapy with Capecitabine and Docetaxel shows promising efficacy as first- line therapy in advanced breast cancer with an acceptable toxicity profile. No significant financial relationships to disclose.
Benign clear cell tumour of the lung--intermediate filament typing as a tool in differential diagnosis
Authors: A Termeer, PM Arkenbout, LK Lacquet, AL Cox
Journal: European Respiratory Journal (1988)

A case of a benign clear cell ('sugar') tumour of the lung in a 61-year-old woman is presented. Characteristic routine histological features are provided and problems concerning differential diagnosis are discussed. Immunohistochemical stainings for the intracytoplasmatic intermediate filament proteins keratin and vimentin in our patient suggest a mesenchymal origin for this rare pulmonary neoplasm, and provide useful diagnostic aid in inconclusive cases.
Patterns of decision making about cancer clinical trial participation among the online cancer treatment community: A collaboration between SWOG and NexCura.
Authors: Joseph M Unger, Dawn L. Hershman, Kenda Burg, Carol Moinpour, Kathy S. Albain, Judith A. Petersen, John Crowley
Journal: Journal of Clinical Oncology (2012)

CRA6009 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News
The Role of Patient Perspectives in Clinical Research Ethics and Policy: Response to Open Peer Commentaries on “Patient Perspectives on the Learning Health System”
Authors: Maureen Kelley, Cyan James, Stephanie Alessi Kraft, Diane Korngiebel, Isabelle Wijangco, Steven Joffe, Mildred K. Cho, Benjamin Wilfond, Sandra Soo-Jin Lee
Journal: The American Journal of Bioethics (2016)
Structural Properties and Tissue Distribution of the Antigen Recognized by the Monoclonal Antibody 653.40S to Human Melanoma Cells&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: P G Natali, K Imai, B S Wilson, A Bigotti, R Cavaliere, M A Pellegrino, S Ferrone
Journal: JNCI Journal of the National Cancer Institute (1981)

The hybridoma 653.40S, constructed with splenocytes from an inbred BALB/c mouse immunized with cultured human melanoma cells, secreted an antibody that had been shown to recognize an antigenic determinant restricted to human melanoma cell lines. The monoclonal antibody (MoAb) 653.40S showed immunoprecipitation of two glycopolypeptides synthesized by melanoma cells, one with the apparent molecular weight of 280,000 and the other one with a molecular weight larger than 500.000. These two glycopolypeptides were not bridged by disulfide bonds and were peripheral rather than integral to the plasma cell membrane. Comparison of the reactivity of cells of the melanocyte lineage with the MoAb 653.40S and with the MoAb Q5/13 to human Ia-like antigens showed that the former reacted with proliferating melanocytes and melanoma cells, whereas the latter reacted only with melanoma cells. The MoAb 653.40S did not react with a large variety of surgically removed normal and tumor tissues except for some instances of basal cell and squamous cell carcinomas. These results suggested that double staining of pigmented skin lesions with the MoAb 653.40S and with an MoAb to Ia-like antigens may help to solve controversial diagnosis of melanoma. Furthermore, the MoAb 653.40S may be useful for radioimaging and immunotherapy of melanoma.
Glucocorticoid Binding Properties of Mouse Thymic Lymphosarcoma Cell Populations Selected for Resistance to the Cytolytic Effects of Glucocorticoids In Vivo&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: A K Chan, E A Thompson
Journal: JNCI Journal of the National Cancer Institute (1983)

Thirteen independently derived murine thymic lymphosarcoma lines were assayed for various aspects of sensitivity to glucocorticoid-induced cytolysis. All tumor lines were sensitive to cytolysis, as evidenced by profound tumor regression after pharmacologic doses of cortisol. All tumor lines contained about 20,000 high-affinity, dexamethasone binding sites/cell. Between 55 and 88% of these presumptive receptor sites underwent nuclear translocation during a 30-minute incubation at 37°C. Dissociation constants (Kd) for the dexamethasone-receptor complex were between 1.5 and 3.6 nM in all cases. Kd for the triamcinolone acetonide-receptor complex were determined for a few tumor lines and were between 0.5 and 0.9 nM. Cytolysis-resistant subpopulations were selected by prolonged glucocorticoid treatment of BALB/Cπ mice bearing tumors from seven of the lymphosarcoma lines. All seven resistant subpopulations contained about 20,000 high-affinity, dexamethasone binding sites/cell. Between 57 and 80% of these presumptive receptor sites underwent nuclear translocation under standard assay conditions. No resistant variants exhibited significantly reduced dexamethasone binding or nuclear translocation properties.
Protein sequence evidence for monophyly of the carnivore families Procyonidae and Mustelidae.
Authors: W W de Jong
Journal: Molecular Biology and Evolution (1986)

The amino acid sequence of the eye lens protein alpha-crystallin A of the ring-tailed cat, Bassariscus astutus, has been determined. The sequence of the Bassariscus alpha A chain, which is 173 residues long, was compared with the previously determined set of 41 mammalian alpha A sequences. Among the investigated carnivores (dog, cat, sloth bear, American mink, gray seal, and California sea lion) the Bassariscus alpha A sequence exclusively shares two amino acid replacements with the alpha A chain of the mink, Mustela vison: 7 His----Gln and 61 Ile----Val. The Mustela and Bassariscus alpha A sequences differ at only three positions and have no replacements in common with any of the other investigated carnivore alpha A chains. Furthermore, the replacement 7 His----Gln has only been found in three-toed sloth, whereas 61 Ile----Val occurs scattered in three other taxa: pig, rhinoceros, and prosimians. It thus is most parsimonious to join Bassariscus and Mustela--and consequently their respective families, Procyonidae and Mustelidae--as sister groups in the phylogenetic tree of mammalian alpha A sequences.
Reactive oxygen species as glomerular autacoids.
Authors: L Baud, B Fouqueray, C Philippe, R Ardaillou
Journal: Journal of the American Society of Nephrology (1992)

There is considerable evidence suggesting that reactive oxygen species (ROS; superoxide anion, hydrogen peroxide, hydroxyl radical, hypochlorous acid) are implicated in the pathogenesis of toxic, ischemic, and immunologically mediated glomerular injury. The capacity of glomerular cells, especially mesangial cells, to generate ROS in response to several stimuli suggests that these autacoids may play a role in models of glomerular injury that are independent of infiltrating polymorphonuclear leukocytes and monocytes. The mechanisms whereby ROS formation results in morphologic lesions and in modifications of glomerular permeability, blood flow, and filtration rate have been inferred from in vitro studies. They involve direct and indirect injury to resident cells (mesangiolysis) and glomerular basement membrane (in concert with metalloproteases) and alteration of both the release and binding of vasoactive substances, such as bioactive lipids (e.g., prostaglandin E2, prostacyclin, thromboxane), cytokines (e.g., tumor necrosis factor alpha), and possibly endothelium-derived relaxing factor. The importance of such processes appears to be modulated by the intrinsic antioxidant defenses of the glomeruli. Further studies are needed to address the role of ROS in human glomerular diseases.
High-dose methotrexate as part of remission maintenance therapy for childhood acute lymphocytic leukemia: a Pediatric Oncology Group pilot study.
Authors: L S Frankel, Y M Wang, J Shuster, R Nitschke, E J Doering, J Pullen
Journal: Journal of Clinical Oncology (1983)

Seventeen children with acute lymphocytic leukemia (ALL) in remission were treated with parenteral high-dose methotrexate (HDM) pulses every eight weeks during standard 6-mercaptopurine and methotrexate (MTX) oral maintenance therapy. MTX (1,000 mg/m2) was infused over one hour followed by one hour of intravenous hydration for the purpose of achieving plasma and cerebrospinal fluid (CSF) levels greater than 10(-6) M for a period of 24 hours. Leucovorin (15 mg/m2) was administered orally six, 12, and 18 hours after completion of the HDM. Plasma and CSF concentrations of MTX were evaluated serially in the first 48 hours. During the first 24 hours, the plasma MTX level was maintained at greater than 10(-6) M. The patients receiving intrathecal MTX at a dose of 15 mg/m2 had an adequate, sustained MTX level in the CSF, but when no intrathecal MTX was administered, the CSF levels were less than 10(-6) M. For that reason, intrathecal MTX in a low dose (6 mg/m2) was injected intrathecally one hour after the HDM infusion, allowing the MTX level in CSF to approximate 10(-6) M over the 24 hours. The toxicity of this therapy was minimal. Due to the facts that the plasma and CSF MTX levels could be sustained above the desired concentrations and this regimen could be given in the outpatient clinic, this program has been incorporated into an ongoing study in an effort to prolong complete remissions.
Studies of the Karyotype of Clonal Strains of Chang Liver Differing in Alkaline-Phospfaatase Activity&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Ursula R. Konigsberg, Ph.D., Harold M. Nitowsky, M.D.
Journal: JNCI Journal of the National Cancer Institute (1962)

Three clonal sublines of Chang liver, which can be distinguished by the activity and thermal stability of alkaline phosphatase in cell-free sonicates, also have characteristic karyotypes. The most unique karyotypic features are the marker chromosomes: the minute metacentric of clone 8A, the large submetacentric of clone 6A, and the absence of both such markers from clone 4. In addition, each clone has a different modal number of total chromosomes, and clone 4 also differs from the other 2 by its lower ratio of metacentric to submetacentric chromosomes. The possible use of these combinations of markers for studies of somatic cell genetics is discussed.
Abstract 3260: Left Atrial Volume Assessment by 3D Echocardiography is Accurate When Compared to MRI in Patients with Acquired Heart Disease and Congenital Heart Disease
Authors: Petra S Niemann, Luiz Pinho, Craig S Broberg, Michael Jerosch-Herold, David J Sahn
Journal: Circulation (2007)

Background: We studied the role of 3D/4D ultrasound (US) for left atrial (LA) volume/function evaluation in patients with coronary artery disease (CAD) and congenital heart disease (CHD). Methods: 22 patients with CAD/CHD were studied with live 3D US and MRI. US images and MRI were obtained at the same visit. US images were acquired with a real time 3D US system (Philips 7500) and X3 matrix-array transducer with full volume sweeps in apical, 4 and 2 chamber views. MR images were acquired with a 1.5/3 T magnet with gradient cine-loop sequencing of the left atrium (LA). US images were analyzed with 4D view software (TomTec) using sagittal/4-chamber/coronal views. LA end diastolic and end systolic volumes (EDV, ESV) and stroke volume (SV) could be measured in all images. MR data were measured offline with Philips MRI software. Results: Regardless of LA shape and size, assessment with 3D US provided images of both the atrial body and appendage in all patients. 3D US results agreed closely with MRI. 3D US measured LA EDV 22.6 ml to 69.8ml, mean = 43.3 ml ± 16.3, while MRI measured LA EDV 20.3 ml to 64 ml, mean = 39.2ml ± 14.4 (r = 0.93). 3D US LA ESV was 14.2ml to 40.7ml, mean = 24.6 ml ± 8.6, while MRI LA ESV was 16.5ml to 41.3 ml, mean = 22.8 ml ± 9.4 (r = 0.95; p &lt; 0.01). Conclusions: Despite the distance from the matrix array in 3D US, it can accurately quantify LA cavity and appendage volume and function.
Surveillance for Possible Estuary-Associated Syndrome—Six States, 1998-1999
Authors: A. L. Hathcock, C. Nace, D. Johnson, R. Quimbo, R. Venezia, A. Chapin, J. S. Cline, K. Buckheit, P. Webb, R. Ball, N. Scruggs, S. Jenkins, L. A. Peipins, M. Monti, M. Brooks
Journal: JAMA (2000)
Identifying benchmarks for ASCO's “Choosing Wisely” measures that address low-value imaging in early-stage prostate and breast cancer.
Authors: Steve Power, Rhonda Lynn Bitting, P. Kelly Marcom, Arif Kamal
Journal: Journal of Clinical Oncology (2013)

194 Background: ASCO has recently selected “Choosing Wisely” measures that identify physician health behaviors of low value in cancer care. Two of these measures address the use of advanced imaging for early stage disease. These measures aim to reduce imaging in patients at low risk for metastatic disease unless there is a clinical indication. To date, no evidence-based benchmarks for meeting these measures have been reported. Methods: We analyzed all patients from January 2010 to June 2012 at the Duke Cancer Institute (DCI), an NCI-designated, comprehensive cancer center. We investigated conformance to two Choosing Wisely measures: avoiding imaging for staging in early stage (ES) prostate cancer (PC) and ES breast cancer (BC). ES was defined by Choosing Wisely as Stage IIb or less for BC and Gleason &lt;7 or PSA &lt;10 ng/mL for PC. Advanced imaging was defined as bone scan, computed tomography (CT) scan, or positron emission tomography (PET) performed at the DCI within 60 days of cancer diagnosis. Descriptive statistics and chi-square were performed. Results: Total 1143 BC and 29 PC were identified. Median age was 58 and 61 years, respectively. 0% (0/29) of PC cases had advanced imaging. Within BC, 20.6% (235/1143) had at least one imaging procedure performed; 16.5% had two or more. Patients with imaging were more likely hormone receptor negative, triple negative, younger (&lt;50), and higher stage (Stage IIb), (all p&lt;0.0001). Of imaging performed in BC, 41% were CT only, 22% were PET or PET/CT, and 36% were bone scans. Ongoing chart abstractions are identifying clinical indications for the ordering of imaging and associated clinical consequences. Conclusions: We have established internal benchmarks for conformance to two Choosing Wisely measures. The lack of advanced imaging for low-risk PC patients demonstrates the feasibility of this measure even in a multi-disciplinary setting. Imaging in &lt;25% low-risk BC patients suggests that these are performed for clinical rather than staging purposes. Further data sharing and comparisons are needed to establish oncology-wide benchmarks.
Protein profiling of tumor tissues by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to discriminate between localized and metastatic renal cell carcinoma
Authors: T. Kamai, N. Tomosugi, H. Abe, K. Yoshida
Journal: Journal of Clinical Oncology (2009)

e16098 Background: We previously reported that mRNA of interferon-alpha receptor type 2 (IFNAR2) was upregulated in metastatic and IFN-a resistant renal cell carcinoma (RCC) in comparison to localized RCC or metastatic tumors with good response to IFN-a (BMC Cancer, 2007). We speculated potential different molecular mechanism between above two groups. Protein profiling using human tumor tissues may give insight into cellular pathways leading to carcinogenesis and metastasis in RCC. Methods: We examined mRNAs expression for IFNAR2 in paired tumor and non-tumor samples from the surgical specimens of Japanese patients with RCC using a real-time reverse transcription polymerase chain reaction. Then we selected representative five IFNAR2 upregulated clear cell carcinomas cases with metastatic tumor, five IFNAR2 upregulated metastatic sarcomatoid carcinomas, and five normal expression clear cell carcinomas with localized tumor. We investigated protein profiling in the tumor tissues of above three groups using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) coupled with IMAC-Cu chips. Results: For hierarchical clustering analysis, we used the 25 peaks which revealed significant differences in single-marker analysis in the range from 1,500 to 10,000 m/z. The heat map analysis based on the clustering distinguished completely metastatic tumors with IFNAR2 upregulated groups from localized tumors with IFNAR2 normal expression group. Furthermore, the heat map discriminated metastatic sarcomatoid carcinomas from metastatic clear cell carcinomas with a sensitivity of 100% and a specificity of 80%. Conclusions: SELDI-TOF MS profiling of tumor tissues can be applied to differentiate patients with three types of RCCs. Our findings may reflect different molecular mechanism between localized and metastatic carcinomas, and the different response to immunotherapy with IFN-α. This may shed light on the potential therapeutic strategy for IFN-α treatment. However, further investigation is required to verify the usefulness of this method in clinical practice. No significant financial relationships to disclose.
High level of divergence of male-reproductive-tract proteins, between Drosophila melanogaster and its sibling species, D. simulans.
Authors: M B Coulthart, R S Singh
Journal: Molecular Biology and Evolution (1988)

We compared male-reproductive-tract polypeptides of Drosophila melanogaster and D. simulans by using two-dimensional gel electrophoresis. Approximately 64% of male-reproductive-tract polypeptides were identical between two randomly chosen isofemale lines from these two species, compared with 83% identity for third-instar imaginal wing-disc polypeptides. Qualitatively similar differences were found between reproductive tracts and imaginal discs when D. sechellia was compared with D. melanogaster and with D. simulans. When genic polymorphism was taken into account, approximately 10% of male-reproductive-tract polypeptides were apparently fixed for different alleles between D. melanogaster and D. simulans; this proportion is the same as that found for soluble enzymes by one-dimensional gel electrophoresis. Strikingly, approximately 20% of male-reproductive-tract polypeptides of either D. melanogaster or D. simulans had no detectable homologue in the other species. We propose that proteins of the Drosophila male reproductive tract may have diverged more extensively between species than have other types of proteins and that much of this divergence may involve large changes in levels of polypeptide expression.