tbuckley/cabot-search huggingface dataset:
Clinical Benefit and Quality of Life in Patients With Advanced Pancreatic Cancer Receiving Gemcitabine Plus Capecitabine Versus Gemcitabine Alone: A Randomized Multicenter Phase III Clinical Trial—SAKK 44/00–CECOG/PAN.1.3.001
Authors: Jürg Bernhard, Daniel Dietrich, Werner Scheithauer, Daniela Gerber, György Bodoky, Thomas Ruhstaller, Bengt Glimelius, Emilio Bajetta, Johannes Schüller, Piercarlo Saletti, Jean Bauer, Arie Figer, Bernhard C. Pestalozzi, Claus-Henning Köhne, Walter Mingrone, Salomon M. Stemmer, Karin Tàmas, Gabriela V. Kornek, Dieter Koeberle, Richard Herrmann
Journal: Journal of Clinical Oncology (2008)

Purpose To compare clinical benefit response (CBR) and quality of life (QOL) in patients receiving gemcitabine (Gem) plus capecitabine (Cap) versus single-agent Gem for advanced/metastatic pancreatic cancer. Patients and Methods Patients were randomly assigned to receive GemCap (oral Cap 650 mg/m 2 twice daily on days 1 through 14 plus Gem 1,000 mg/m 2 in a 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m 2 in a 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks) for 24 weeks or until progression. CBR criteria and QOL indicators were assessed over this period. CBR was defined as improvement from baseline for ≥ 4 consecutive weeks in pain (pain intensity or analgesic consumption) and Karnofsky performance status, stability in one but improvement in the other, or stability in pain and performance status but improvement in weight. Results Of 319 patients, 19% treated with GemCap and 20% treated with Gem experienced a CBR, with a median duration of 9.5 and 6.5 weeks, respectively (P &lt; .02); 54% of patients treated with GemCap and 60% treated with Gem had no CBR (remaining patients were not assessable). There was no treatment difference in QOL (n = 311). QOL indicators were improving under chemotherapy (P &lt; .05). These changes differed by the time to failure, with a worsening 1 to 2 months before treatment failure (all P &lt; .05). Conclusion There is no indication of a difference in CBR or QOL between GemCap and Gem. Regardless of their initial condition, some patients experience an improvement in QOL on chemotherapy, followed by a worsening before treatment failure.
Liposome-Mediated Modulation of Multidrug Resistance in Human HL-60 Leukemia Cells
Authors: Aquilur Rahman, Syed R. Husain, Javed Siddiqui, Madhu Verma, Michael Agresti, Melvin Center, Ahmad R. Safa, Robert I. Glazer
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Liposome-Mediated Modulation of Multidrug Resistance in Human HL-60 Leukemia Cells Get access Aquilur Rahman, Aquilur Rahman Search for other works by this author on: Oxford Academic PubMed Google Scholar Syed R. Husain, Syed R. Husain Search for other works by this author on: Oxford Academic PubMed Google Scholar Javed Siddiqui, Javed Siddiqui Search for other works by this author on: Oxford Academic PubMed Google Scholar Madhu Verma, Madhu Verma Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Agresti, Michael Agresti Search for other works by this author on: Oxford Academic PubMed Google Scholar Melvin Center, Melvin Center Search for other works by this author on: Oxford Academic PubMed Google Scholar Ahmad R. Safa, Ahmad R. Safa Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert I. Glazer Robert I. Glazer Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 24, 16 December 1992, Pages 1909–1915, https://doi.org/10.1093/jnci/84.24.1909 Published: 16 December 1992 Article history Received: 27 February 1992 Revision received: 14 September 1992 Accepted: 23 September 1992 Published: 16 December 1992
Radiation leukemia in C57BL/6 mice. II. Lack of ecotropic virus expression in the majority of lymphomas.
Authors: J N Ihle, D R Joseph, N H Pazmino
Journal: The Journal of Experimental Medicine (1976)

The expression of endogenous ecotropic viruses in radiation-induced thymomas of C57BL/6 mice was examined. Competition radioimmunoassays for AKR MuLV gp71, p30, and p12 were used for viral antigen expression. 3 of 40 lymphomas had readily detectable ecotropic gp71 at levels of 95-689 ng/mg protein; the remainder of the tumors had no detectable gp71 (less than 1.0 ng/mg protein). 30 thymomas were characterized by the presence of MuLV p30 at levels of 1-10 ng/mg protein, levels that were comparable to those found in thymus extracts from age-matched, nonirradiated control. 10 tumors were characterized by having p30 levels of 10-30 ng/mg protein. In one tumor significant levels of AKR MuLV p12 were detectable. Since B-tropic and N-tropic viruses from C57BL/6 mice have glycoproteins (gp71) indistinguishable from AKR MuLV gp71 and the N-tropic virus had a p12 serologically identical to AKR MuLV p12, these results demonstrate that overt endogenous B-tropic virus was detectable in 2 of 40 thymomas and endogenous N-tropic virus was detectable in 1 of 40 thymomas. The lack of overt expression of gp71 or p12 was also confirmed by cytotoxicity assays using monospecific antisera to these viral proteins. Radiation-induced lymphomas were also examined for the presence of reverse transcriptase after chromatography of tissue extracts on poly G-Sepharose. One tumor, which was characterized by the lack of gp71, also had no detectable reverse transcriptase; whereas one tumor with gp71 was characterized by readily detectable levels of reverse transcriptase in cellular extracts. The presence of viral RNA was examined using AKR cDNA. Low levels of RNA capable of hybridizing with AKR cDNA were found in age-matched, nonirradiated mice; these hybrids had Tm's of 72 degrees C, while hybrids with AKR MuLV 70S RNA had Tm's of 80 degrees C. In 1 of 12 thymomas the concentration of hybridizable RNA and the Tm of the hybrids were identical to control values. In 9 of 12 thymomas the concentration of hybridizable sequences increased approximately three-to fivefold and the Tm of these hybrids varied from 73 to 75 degrees C. In 1 of 12 thymomas the concentration of hybridizable sequences increased over 100-fold, hybridized completely with AKR MuLV cDNA, and the hybrids had Tm's of 79 degrees C. This thymoma was also characterized by the presence of the AKR MuLV type of gp71 and p12. One tumor was characterized by a 10-to 100-fold increase in hybridizable sequences, which only partially hybridized with AKR MuLV cDNA, and hybrids had a Tm of 73 degrees C. This tumor was characterized by the presence of AKR MuLV gp71 but not AKR MuLV p12. The results taken together demonstrate that overt endogenous ecotropic virus expression is only rarely detectable in radiation-induced thymomas of C57BL/6 mice.
The Vascular Stapler in Transplantation Surgery
Authors: Donald R. Becker
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Lindsey et al recently commented, in these pages, upon the value of the vascular stapler in clinical renal transplantation (<b>205</b>: 180, 1968). They emphasized the value of a stapler in reducing the ischemia time to the transplanted kidney. We have had considerable experience with the use of the stapler in performing rabbit renal transplants.<sup>1</sup>This experience sharpened our interest in the use of this type of instrument in small vessel surgery. The following case demonstrates a circumstance in which familiarity with stapling instruments can be used advantageously. <h3>Report of a Case:—</h3> The patient was a 19-year-old female who came to receive a renal allograft after several months of preparatory dialysis and study. Her father was the kidney donor. Arteriography showed that the vasculature to each of his kidneys was anomalous (Fig 1). His left kidney was supplied by two renal arteries of almost equal size. His
Possible Association of Trisomy 8 with Secondary Pulmonary Alveolar Proteinosis in Myelodysplastic Syndrome
Authors: Aya Nishida, Atsushi Miyamoto, Hisashi Yamamaoto, Naoyuki Uchida, Koji Izutsu, Atsushi Wake, Yasunori Ohta, Takeshi Fujii, Hideki Araoka, Shuichi Taniguchi, Kazuma Kishi
Journal: American Journal of Respiratory and Critical Care Medicine (2011)
Effects of a novel tyrosine kinase inhibitor in rheumatoid arthritis synovial fibroblasts
Authors: L C Huber, P Kunzler, S H Boyce, B A Michel, R E Gay, B S Ink, S Gay
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> Biologicals have revolutionised the treatment of rheumatoid arthritis (RA). However, progressive joint destruction can still be observed in many patients and the search for novel molecular therapies targeting specific signalling pathways is ongoing. In the present study, we investigated the effects of GW282974, a novel compound directed against tyrosine kinase activity with respect to the potential suppression of inflammation and destruction. <h3>Methods:</h3> Synovial tissue specimens were obtained from RA patients undergoing surgical joint replacement. Rheumatoid arthritis synovial fibroblasts (RASFs) were stimulated with cytokines and GW282974 was added in different concentrations. Gene expression was checked by TaqMan PCR, using 18S as housekeeping gene. Protein analysis was quantified by ELISA. Cell growth and proliferation was measured using the “ViaLight” proliferation assay. <h3>Results:</h3> EGF had no effect on the gene expression profile of RASFs when used as single stimulatory agent. In combination with pro-inflammatory mediators however, EGF showed a synergistic effect. The expression of matrix metalloproteinases, inflammatory cytokines and cyclooxygenase-2 on mRNA levels was strongly increased, whereas the addition of GW282974 abrogated these effects in a dose-dependent manner. These data could be confirmed on protein/lipid levels analysing the supernatants of RASFs by ELISA. Similarly, cell growth and proliferation of RASFs were inhibited by GW282974 in a dose- and time-dependent manner. By contrast, no cytotoxic effects were seen within the concentrations used. <h3>Discussion:</h3> GW282974 appears to interfere with the inflammatory and the destructive pathways in RASFs and might therefore be used as novel therapeutic strategy for the treatment of RA.
Chemokine Receptor<i>CXCR4</i>Expression in Colorectal Cancer Patients Increases the Risk for Recurrence and for Poor Survival
Authors: Joseph Kim, Hiroya Takeuchi, Stella T. Lam, Roderick R. Turner, He-Jing Wang, Christine Kuo, Leland Foshag, Anton J. Bilchik, Dave S.B. Hoon
Journal: Journal of Clinical Oncology (2005)

Liver metastasis is the predominant cause of colorectal cancer (CRC) related mortality. Chemokines, soluble factors that orchestrate hematopoetic cell movement, have been implicated in directing cancer metastasis, although their clinical relevance in CRC has not been defined. Our hypothesis was that the chemokine receptor CXCR4 expressed by CRC is a prognostic factor for poor disease outcome.CRC cell lines (n = 6) and tumor specimens (n = 139) from patients with different American Joint Committee on Cancer (AJCC) stages of CRC were assessed. Microarray screening of select specimens and cell lines identified CXCR4 as a prominent chemokine receptor. CXCR4 expression in tumor and benign specimens was assessed by quantitative real-time reverse transcription polymerase chain reaction and correlated with disease recurrence and overall survival.High CXCR4 expression in tumor specimens (n = 57) from AJCC stage I/II patients was associated with increased risk for local recurrence and/or distant metastasis (risk ratio, 1.35; 95% CI, 1.09 to 1.68; P = .0065). High CXCR4 expression in primary tumor specimens (n = 35) from AJCC stage IV patients correlated with worse overall median survival (9 months v 23 months; RR, 2.53; 95% CI, 1.19 to 5.40; P = .016). CXCR4 expression was significantly higher in liver metastases (n = 39) compared with primary CRC tumors (n = 100; P < .0001).CXCR4, a well-characterized chemokine receptor for T-cells, is differentially expressed in CRC. CXCR4 gene expression in primary CRC demonstrated significant associations with recurrence, survival, and liver metastasis. The CXCR4-CXCL12 signaling mechanism may be clinically relevant for patients with CRC and represents a potential novel target for disease-directed therapy.
Alternate Splicing of the p53 Inhibitor HDMX Offers a Superior Prognostic Biomarker than p53 Mutation in Human Cancer
Authors: Kristiaan Lenos, Anna M. Grawenda, Kirsten Lodder, Marieke L. Kuijjer, Amina F.A.S. Teunisse, Emmanouela Repapi, Lukasz F. Grochola, Frank Bartel, Pancras C.W. Hogendoorn, Peter Wuerl, Helge Taubert, Anne-Marie Cleton-Jansen, Gareth L. Bond, Aart G. Jochemsen
Journal: Cancer Research (2012)

Conventional high-grade osteosarcoma is the most common primary bone malignancy. Although altered expression of the p53 inhibitor HDMX (Mdmx/Mdm4) is associated with cancer risk, progression, and outcome in other tumor types, little is known about its role in osteosarcoma. High expression of the Hdmx splice variant HDMX-S relative to the full-length transcript (the HDMX-S/HDMX-FL ratio) correlates with reduced HDMX protein expression, faster progression, and poorer survival in several cancers. Here, we show that the HDMX-S/HDMX-FL ratio positively correlates with less HDMX protein expression, faster metastatic progression, and a trend to worse overall survival in osteosarcomas. We found that the HDMX-S/HDMX-FL ratio associated with common somatic genetic lesions connected with p53 inhibition, such as p53 mutation and HDM2 overexpression in osteosarcoma cell lines. Interestingly, this finding was not limited to osteosarcomas as we observed similar associations in breast cancer and a variety of other cancer cell lines, as well as in tumors from patients with soft tissue sarcoma. The HDMX-S/HDMX-FL ratio better defined patients with sarcoma with worse survival rates than p53 mutational status. We propose a novel role for alternative splicing of HDMX, whereby it serves as a mechanism by which HDMX protein levels are reduced in cancer cells that have already inhibited p53 activity. Alternative splicing of HDMX could, therefore, serve as a more effective biomarker for p53 pathway attenuation in cancers than p53 gene mutation.
Dose-Response Study of Recombinant Factor VIIa/Tissue Factor Inhibitor Recombinant Nematode Anticoagulant Protein c2 in Prevention of Postoperative Venous Thromboembolism in Patients Undergoing Total Knee Replacement
Authors: Agnes Lee, Giancarlo Agnelli, Harry Büller, Jeffrey Ginsberg, John Heit, William Rote, George Vlasuk, Lorrie Costantini, Jim Julian, Philip Comp, Jan van der Meer, Franco Piovella, Gary Raskob, Michael Gent
Journal: Circulation (2001)

With the best prophylactics now available, venous thromboembolism after total knee replacement remains substantial (25% to 27%). Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent inhibitor of factor VIIa/tissue factor complex that has the potential to reduce this risk. The present study was performed to determine an efficacious and safe dose of rNAPc2 for prevention of venous thromboembolism after elective, unilateral total knee replacement.This open-label, sequential dose-ranging study was conducted in 11 centers in Canada, Europe, and the United States. Five regimens were tested. Injections were administered subcutaneously on the day of surgery (day 1) and days 3, 5, and optionally, day 7. Primary efficacy outcome was a composite of overall deep vein thrombosis based on mandatory unilateral venography (day 7+/-2) and confirmed symptomatic venous thromboembolism recorded </=48 hours after the last dose of rNAPc2. Primary safety outcome was major bleeding </=72 hours after the last dose. An independent, blinded Central Adjudication Committee assessed all outcome events. Of 293 patients studied, 251 (86%) could be evaluated for primary efficacy analysis. A dosage of 3.0 microgram/kg administered within 1 hour after surgery provided the best observed results, with an overall deep vein thrombosis rate of 12.2%, a proximal deep vein thrombosis rate of 1.3%, and a major bleeding rate of 2.3%.A randomized, double-blind trial that compared rNAPc2 with current best prophylactics is warranted based on encouraging, first-reported clinical results for a factor VIIa/tissue factor inhibitor evaluated for thrombosis prophylaxis.
Theranostic Imaging of the Kinases and Proteases that Modulate Cell Death and Survival
Authors: Howard H. Chen, Hushan Yuan, Lee Josephson, David E. Sosnovik
Journal: Theranostics (2012)

Several signaling cascades are involved in cell death, with a significant amount of crosstalk between them.Despite the complexity of these cascades several key pro-survival and pro-death players have been identified.These include PI3-kinase, AKT and caspase-3.Here we review the approaches used to date to perform molecular imaging of these important targets.We focus in particular on approaches that include the possibility of modulating the activity of these kinases and proteases in a theranostic approach.
Mortality by Race Among Low-Income Adults With Early-Onset Insulin-Treated Diabetes
Authors: Baqiyyah Nilija Conway, Thomas Anais Elasy, Michael E. May, William James Blot
Journal: Diabetes Care (2013)

To determine if long-term mortality rates in early-onset insulin-treated diabetes differ by race among adults of similar socioeconomic status.A total of 391 (299 African Americans, 92 whites) mostly low-income adults 40-79 years of age with insulin-treated diabetes diagnosed before 30 years of age were recruited from community health centers in the southeast U.S. Cox models were used to estimate hazard ratios (HRs) of all-cause mortality among African Americans compared with whites. Additionally, standardized mortality ratios (SMRs) were used to compare the mortality experience of the individuals with diabetes with both national and general community health center sex- and race-specific population norms.Mean age at diabetes diagnosis and cohort entry, respectively, was 21 and 50 years in African Americans and 19 and 51 years in whites. During an average of 6.7 years of follow-up, 29% of African Americans and 35% of whites died. In multivariable analysis, no significant mortality difference was observed among African Americans compared with whites (HR 0.83 [95% CI 0.53-1.30]; P=0.51). Compared with the race-specific U.S. general population, SMRs for those with diabetes were 5.7 in African Americans and 11.7 in whites. However, when compared with the same source population (i.e., the community health center population), SMRs were 3.5 and 3.7 in African Americans and whites, respectively.Elevated mortality persists in men and women with long duration of early-onset insulin-treated diabetes, but given survival to 40 years of age and similarly low economic status and access to health care, our data do not suggest a racial disparity in mortality.
Sodium Diphenyl Hydantoinate in the Treatment of Convulsive Disorders
Authors: H. H. Merritt, T. J. Putnam
Journal: JAMA (1984)

Good results in the treatment of patients with convulsive seizures have been obtained by a variety of methods, such as medical treatment with bromides or barbituric acid compounds, the ketogenic diet, restriction of fluids, and the surgical excision of scars or irritable cortical foci. In spite of these various therapeutic means there are a great number of patients who are not relieved of their attacks or are helped only temporarily by treatment. The fact that treatment by anticonvulsant drugs is at present the most widely used and on the whole the most effective method of therapy suggested to us the possibility that a direct and systematic experimental search might reveal more potent and less sedative compounds. With this idea in mind we devised an experimental procedure<sup>1</sup>which would produce convulsive seizures in animals at a constant threshold andwhich would allow for a qualitative and roughly quantitative determination of
Increased FOG-2 in Failing Myocardium Disrupts Thyroid Hormone–Dependent SERCA2 Gene Transcription
Authors: Rosanne Rouf, Sarah Greytak, Eric C. Wooten, Jing Wu, Jay Boltax, Michael Picard, Eric C. Svensson, Wolfgang H. Dillmann, Richard D. Patten, Gordon S. Huggins
Journal: Circulation Research (2008)

Reduced expression of sarcoplasmic reticulum calcium ATPase (SERCA)2 and other genes in the adult cardiac gene program has raised consideration of an impaired responsiveness to thyroid hormone (T3) that develops in the advanced failing heart. Here, we show that human and murine cardiomyopathy hearts have increased expression of friend of GATA (FOG)-2, a cardiac nuclear hormone receptor corepressor protein. Cardiac-specific overexpression of FOG-2 in transgenic mice led to depressed cardiac function, activation of the fetal gene program, congestive heart failure, and early death. SERCA2 transcript and protein levels were reduced in FOG-2 transgenic hearts, and FOG-2 overexpression impaired T3-mediated SERCA2 expression in cultured cardiomyocytes. FOG-2 physically interacts with thyroid hormone receptor-alpha1 and abrogated even high levels of T3-mediated SERCA2 promoter activity. These results demonstrate that SERCA2 is an important target of FOG-2 and that increased FOG-2 expression may contribute to a decline in cardiac function in end-stage heart failure by impaired T3 signaling.
A Phase I/II Trial Combining High-Dose Melphalan and Autologous Transplant with Bortezomib for Multiple Myeloma: A Dose- and Schedule-Finding Study
Authors: Sagar Lonial, Jonathan Kaufman, Mourad Tighiouart, Ajay Nooka, Amelia A. Langston, Leonard T. Heffner, Claire Torre, Stephanie McMillan, Heather Renfroe, R. Donald Harvey, Mary J. Lechowicz, H. Jean Khoury, Christopher R. Flowers, Edmund K. Waller
Journal: Clinical Cancer Research (2010)

We did a randomized phase I/II trial designed to evaluate the safety and efficacy of combining the proteasome inhibitor bortezomib with high-dose melphalan as the conditioning for high-dose therapy and autologous transplant for myeloma.Enrolled patients were limited to those who did not achieve a very good partial remission (VGPR) following one or more induction regimens, and were randomized to receive a single escalating dose of bortezomib (1.0, 1.3, or 1.6 mg/m(2)) either 24 hours before or 24 hours after high-dose melphalan. Dose escalation was based on the escalation with overdose control (EWOC), a Bayesian statistical model. Bone marrow aspirates were collected before initiation of therapy and at the time of transplant to evaluate which sequence resulted in maximal plasma cell apoptosis, and response to transplant was assessed by the International Myeloma Working Group criteria.Among 39 randomized patients, 20 received bortezomib after melphalan and 19 received bortezomib before melphalan. Toxicities and posttransplant hematopoietic recovery rates were similar between arms. The overall response rate for all patients was 87%, with 51% achieving a VGPR or better. Pharmacodynamic studies showed greater plasma cell apoptosis among patients who received bortezomib following melphalan.The use of bortezomib in conjunction with high-dose melphalan is safe, with data suggesting improved efficacy. A single dose of bortezomib administered after high-dose melphalan is the recommended dose and schedule for future clinical investigation.