tbuckley/cabot-search huggingface dataset:
Liver and Forestomach Tumors and Other Forestomach Lesions in Rats Treated With Morpholine and Sodium Nitrite, With and Without Sodium Ascorbate&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: Sidney S. Mirvish, Shahrokh Salmasi, Samuel M. Cohen, Kashinath Patil, Ezzat Mahboubi
Journal: JNCI Journal of the National Cancer Institute (1983)

Administration to rats of ascorbate with morpholine and nitrite was previously shown to inhibit the liver tumor production and to enhance the induction of forestomach tumors, as compared to treatment with morpholine and nitrite. In a repetition of this experiment, 10 g morpholine/kg in the diet and 2 g sodium nitrite/liter in the drinking water were administered for life to male MRC-Wistar rats without (group 1) or with (group 2) 22.7 g sodium ascorbate/kg in the diet. Group 3 was untreated. Group 2 showed a lower liver tumor incidence with a longer latency than group 1, indicating a 78% inhibition by ascorbate of in vivo N-nitrosomorpholine (NMOR) formation. The incidence of forestomach papillomas was 3% in group 1, 38% in group 2, and 8% in group 3. The difference between groups 1 and 2 was not significant due to the shorter life-span of group 1. Group 1 and especially group 2 had more forestomach hyperplasia and hyperkeratosis than group 3. Ascorbate might have enhanced induction of these lesions because of an action synergistic with that of NMOR. However, it is most likely that the lowered NMOR dose and concomitantly increased survival produced by the ascorbate were solely responsible for the increased incidence of forestomach papillomas and other lesions in group 2.
N-Terminal Pro–B-Type Natriuretic Peptide for Risk Assessment in Patients With Atrial Fibrillation
Authors: Ziad Hijazi, Lars Wallentin, Agneta Siegbahn, Ulrika Andersson, Christina Christersson, Justin Ezekowitz, Bernard J. Gersh, Michael Hanna, Stefan Hohnloser, John Horowitz, Kurt Huber, Elaine M. Hylek, Renato D. Lopes, John J.V. McMurray, Christopher B. Granger
Journal: Journal of the American College of Cardiology (2013)
Phase I and Pharmacokinetic Study of BMS-184476, a Taxane With Greater Potency and Solubility Than Paclitaxel
Authors: Manuel Hidalgo, Cheryl Aylesworth, Lisa A. Hammond, Carolyn D. Britten, Geoffrey Weiss, Joseph Stephenson, Garry Schwartz, Amita Patnaik, Lon Smith, Kathleen Molpus, Sally Felton, Elora Gupta, Karen J. Ferrante, Anne Tortora, Daryl S. Sonnichsen, Jamey Skillings, Eric K. Rowinsky
Journal: Journal of Clinical Oncology (2001)

To assess the feasibility, toxicity, pharmacokinetics, and preliminary activity of BMS-184476 administered as a 1-hour intravenous (IV) infusion every 3 weeks.Patients with advanced solid malignancies were treated with escalating doses of BMS-184476 as a 1-hour IV infusion every 3 weeks without premedication to prevent hypersensitivity reactions (HSR). Plasma sampling and urine collections were performed to characterize the pharmacokinetics and pharmacodynamics of BMS-184474.Thirty-four patients were treated with 78 courses of BMS-184476 at five dose levels ranging from 20 to 80 mg/m2. Dose-limiting toxicity (DLT), consisting of severe neutropenia with fever, severe diarrhea, and/or severe mucositis, was experienced during course 1 by six of nine minimally pretreated patients treated at the 70 and 80 mg/m2 dose level. In contrast, of 15 assessable patients treated at the 60 mg/m2 dose level, which is the maximum-tolerated dose (MTD) of BMS-184476 on this administration schedule, only one heavily pretreated patient developed DLT (grade 4 neutropenia with fever and grade 3 diarrhea). One patient developed a grade 2 HSR during a second course of BMS-184476 at the 40 mg/m2 dose level. A previously untreated patient with an advanced cholangiocarcinoma experienced a partial response, and a patient with an untreated carcinoma of the gastroesophageal junction had a minor response. The pharmacokinetics of BMS-184476 seemed linear in the dose range studied. Mean +/- SD values for clearance, volume of distribution at steady-state, and terminal half-life were 220 +/- 89 mL/min/m2, 402 +/- 231 L/m2, and 40.8 +/- 21.8 hours, respectively.The MTD and recommended dose for phase II evaluations of BMS-184476 is 60 mg/m2 as a 1-hour IV infusion every 3 weeks. The results of this study suggest that BMS-184476 may have several advantages compared with paclitaxel in terms of toxicity, pharmacokinetics, pharmaceutics, and administration and warrants further clinical development.
Eltrombopag in thrombocytopenic patients with advanced myelodysplastic syndromes (MDS) or secondary acute myeloid leukemia after MDS: A phase I/II study.
Authors: S. Wroblewski, W. Shi, P. Mudd, M. Aivado
Journal: Journal of Clinical Oncology (2010)

TPS184 Background: Patients with myelodysplastic syndromes (MDS) frequently develop thrombocytopenia for which the only effective treatment is repeated platelet transfusions. Eltrombopag is an orally available, nonpeptide thrombopoietin receptor (TPO-R) agonist that increases platelet counts by binding the transmembrane domain of TPO-R, and is approved for the treatment of chronic immune thrombocytopenic purpura. In vitro preclinical studies in leukemia and lymphoma cell lines and patient samples indicate that eltrombopag does not stimulate, and may suppress, leukemic cell growth (Erickson-Miller 2007; Will 2009). The objective of this study is to assess safety, tolerability, and efficacy of eltrombopag. In addition, platelet production, the impact on bleeding, platelet transfusion use, and patient survival will be evaluated. Methods: This multicenter, double-blind, randomized, placebo-controlled, 6-month study is enrolling adult patients with advanced MDS or secondary acute myeloid leukemia after MDS (sAML/MDS). Patients with 20–50% bone marrow blasts, who are relapsed, refractory, or ineligible to receive standard therapies (azacitidine, decitabine, intensive chemotherapy, stem cell transplantation) are eligible. Patients must have platelet counts <30,000/μ L or be platelet transfusion-dependent. Up to 90 patients will be enrolled and safety and efficacy data from ∼60 evaluable subjects will be analyzed to determine an optimal dose. Oral eltrombopag will be administered initially at 50 mg once daily, with intra-individual stepwise dose adjustments up to 300 mg, based on platelet counts and bone marrow blast counts. Patients will be randomized 2:1 (eltrombopag:placebo) and would receive best supportive care. The primary endpoint of the study is safety and tolerability assessed by adverse events and bone marrow blast counts. Secondary endpoints include platelet response, frequency and number of platelet transfusions, duration of platelet transfusion- independence, incidence and severity of bleeding, overall survival, and pharmacokinetics. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline
Impact of Surgical and Pathologic Variables in Rectal Cancer: A United States Community and Cooperative Group Report
Authors: Luca Stocchi, Heidi Nelson, Daniel J. Sargent, Michael J. O’Connell, Joel E. Tepper, James E. Krook, Robert Beart
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Substantial and successful effort has been focused on decreasing the risk of local failure after rectal cancer surgery through the use of adjuvant therapies. Our study examined data from studies conducted by United States cooperative groups to investigate the impact of surgical and pathologic variables in rectal cancer outcomes. PATIENTS AND METHODS: Surgical and pathologic reports from 673 patients with stage II/III rectal cancer enrolled onto three adjuvant clinical trials were reviewed for tumor and surgical variables. Additional information on individual institutions and operating surgeon was collected. Variables were tested for association with 5-year local recurrence and survival after adjustment for adjuvant treatments and other important prognostic factors. RESULTS: Five-year local recurrence and survival rates were 16% and 59%, respectively. Surgeons treating more than 10 study cases had lower local recurrence rates than those treating ≤ 10 (11% v 17%, P = .02). Free radial margins also correlated with local recurrence (P = .01). Type of surgery, distal margins, and tumor radial spread were not significant. Tumor adherence to adjacent structures predicted local recurrence (35% v 14%, P &lt; .001) and survival (30% v 63%, P &lt; .001), regardless of en bloc resection. Although T and N classification predicted survival (P &lt; .001), only N classification correlated with local recurrence. The number and percentage of positive nodes correlated with survival, but only the percentage independently predicted local recurrence. Several pathologic and surgical variables were reported suboptimally. CONCLUSION: Moderate variability in outcomes among surgeons was detected in this high-risk population. Efforts to improve surgical results will require changes in reporting practices to allow for more accurate assessment of the quality of surgery.
Segmental pigmentation disorder - response: reply from authors
Authors: M. Hogeling, I.J. Frieden
Journal: British Journal of Dermatology (2010)

Journal Article Segmental pigmentation disorder – response: reply from authors Get access M. Hogeling, M. Hogeling Department of Paediatric Dermatology, Sydney Children’s Hospital, Randwick 2031, Australia Search for other works by this author on: Oxford Academic Google Scholar I.J. Frieden I.J. Frieden Department of Dermatology, University of California, San Francisco, CA 94115, U.S.A. E‐mail: hogelingm@yahoo.ca Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 1, 1 January 2011, Pages 226–227, https://doi.org/10.1111/j.1365-2133.2010.10075.x Published: 01 January 2011
Epstein-Barr Virus and Nasopharyngeal Carcinoma: Is There an Etiologic Relationship?2
Authors: B. E. Henderson, E. W. Louie, J. S. Jing, B. Alena
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Epstein-Barr Virus and Nasopharyngeal Carcinoma: Is There an Etiologic Relationship? Get access B. E. Henderson, B. E. Henderson Search for other works by this author on: Oxford Academic PubMed Google Scholar E. W. Louie, E. W. Louie Search for other works by this author on: Oxford Academic PubMed Google Scholar J. S. Jing, J. S. Jing Search for other works by this author on: Oxford Academic PubMed Google Scholar B. Alena B. Alena Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 5, November 1977, Pages 1393–1395, https://doi.org/10.1093/jnci/59.5.1393 Published: 01 November 1977 Article history Received: 09 March 1977 Accepted: 21 June 1977 Published: 01 November 1977
Modification of Pancreatic Carcinogenesis in the Hamster Model. X. Effect of Streptozotocin&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 M Pour, K Patil
Journal: JNCI Journal of the National Cancer Institute (1983)

An experiment was conducted to examine the possibility that the carcinogenic effect on the pancreas of streptozotocin (SZ) and N-nitrosobis(2-oxopropyl)amine (BOP) is based on similar mechanisms; groups of outbred Syrian golden hamsters were treated with SZ (single iv injection, 30 mg/kg body wt) alone, BOP alone (single sc injection, 10 mg/kg body wt), and SZ and BOP simultaneously. The experiment was terminated 52 weeks after treatment began. Of the hamsters treated with SZ alone, 44% developed islet cell tumors, most of which were of pleomorphic cell types. In addition, 40% of the hamsters developed pseudoductules and 12% developed ductular adenomas. The carcinogenicity of SZ for the exocrine pancreas was further indicated by induction of ductular carcinomas by SZ plus BOP, the incidence of which was significantly higher (P less than .0001) than that induced by BOP alone.
Kinetics of organ response and survival following normalization of the serum free light chain ratio in AL amyloidosis
Authors: Gregory P. Kaufman, Angela Dispenzieri, Morie A. Gertz, Martha Q. Lacy, Francis K. Buadi, Suzanne R. Hayman, Nelson Leung, David Dingli, John A. Lust, Yi Lin, Prashant Kapoor, Ronald S. Go, Steven R. Zeldenrust, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar
Journal: American Journal of Hematology (2014)

Despite successful treatment of the clonal plasma cell implicated in its pathogenesis, patients with AL amyloidosis (AL) experience significant morbidity related to underlying amyloid mediated organ dysfunction. While normalization of the serum free light chain measurements [normal ratio of involved and uninvolved free light chains (nFLCr)] is the goal of therapy and centerpiece of hematologic response criteria, achieving (or not achieving) meaningful organ response (OR) is clinically significant for its implications on long-term symptomatology as well as overall survival (OS), and remains the ultimate goal of treatment. Expectations for organ recovery following successful therapy leading to nFLCr in AL remain poorly described. We evaluated the timeframe and predictive factors for OR, and long-term outcome, in 313 AL patients who achieved nFLCr following therapy initiation. OR was seen in 80% of surviving AL patients within 1-year of nFLCr. Patients achieving early OR within 1 year of nFLCr had superior OS compared with those who despite obtaining nFLCr did not achieve early OR. We further evaluated factors predicting OR and OS among patients achieving nFLCr. Higher values of dFLC (involved-uninvolved) at diagnosis predict OR, and early OR predicts improved OS following successful hematologic therapy in AL.
Diet, nutrition, and cancer: Interim dietary guidelines
Authors: S Palmer, K Bakshi
Journal: JNCI Journal of the National Cancer Institute (1983)

The Committee on Diet, Nutrition, and Cancer of the National Academy of Sciences recently evaluated the role of diet in carcinogenesis. Both epidemiological and laboratory evidence suggests that a high intake of total fat increases susceptibility to cancer of different sites, particularly the breast and colon. In epidemiological studies frequent consumption of certain fruits and vegetables and in laboratory experiments some components of fruits and vegetables, especially cruciferous vegetables, appear to decrease the incidence of cancers at various sites. In contrast, frequent consumption of salt-cured, salt-pickled, or smoked foods, possibly because they may contain nitrosamines or polycyclic aromatic hydrocarbons, appears to increase the risk of esophageal or stomach cancer. Excessive alcohol consumption among smokers appears to be associated with an elevated risk of cancers of the oral cavity, esophagus, larynx, and respiratory tract. Interim dietary guidelines to reduce the risk of cancer were proposed in accordance with these conclusions. No definitive conclusions were reached for other dietary factors, including total calories, cholesterol, fiber, and selenium, nor could the quantitative contribution of diet to overall cancer risk be estimated.
Quinidine as a resistance modulator of epirubicin in advanced breast cancer: mature results of a placebo-controlled randomized trial.
Authors: G C Wishart, D Bissett, J Paul, D Jodrell, A Harnett, T Habeshaw, D J Kerr, M A Macham, M Soukop, R C Leonard
Journal: Journal of Clinical Oncology (1994)

PURPOSE To evaluate the effect of quinidine, a putative modulator of P-glycoprotein-mediated drug resistance, on the response rate and toxicity profile of epirubicin in patients with advanced breast cancer. PATIENTS AND METHODS Between 1989 and 1992, 223 eligible patients were randomized in double-blind fashion to receive epirubicin 100 mg/m2 by intravenous (i.v.) bolus and prednisolone 25 mg orally twice daily, along with either placebo or quinidine (250 mg) capsules, taken for 4 days before and 2 days after chemotherapy. Treatment was continued for a maximum of eight courses. RESULTS Ten eligible patients did not complete the first cycle of treatment. Of the remaining patients, 106 in the placebo arm received 619 courses of treatment, and 107 in the quinidine arm received 612 courses. The median cumulative dose of epirubicin in both arms was 600 mg/m2. The median quinidine level (measured before epirubicin administration in 288 courses) was 5.5 mumol/L; at this concentration, the drug partially reverses anthracycline resistance in multidrug-resistant (MDR) breast carcinoma cells in vitro. There were no statistically significant differences in hematologic or gastrointestinal toxicity between the two arms. The response rate in the placebo arm was 44% (6% complete remission [CR], 38% partial remission [PR]), and in the quinidine arm was 43% (4% CR, 39% PR). Surviving patients have been monitored for a median time of 74 weeks, and there is no significant difference in the overall or progression-free survival between the two arms. The median survival times were 59 weeks for placebo and 47 weeks for quinidine patients. The estimated relative death rate (quinidine/placebo) was 1.2 (P = .247; 95% confidence interval [CI], 0.88 to 1.63). CONCLUSION Quinidine at this dose does not significantly alter the toxicity profile, response rate, or survival after epirubicin chemotherapy in patients with advanced breast cancer. This may be due to ineffective modulation of P-glycoprotein by quinidine or the lack of expression of mdr-1 in a sufficient proportion of cells in these tumors, or alternative mechanisms underlying resistance to epirubicin.
Concomitant Loss of Specific Cell-Surface Antigen and Demonstrable Type-C Virus Particles in Lymphomas Induced by Radiation Leukemia Virus in Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Jorge F. Ferrer, Frederic A. Gibbs
Journal: JNCI Journal of the National Cancer Institute (1969)

Examined were the antigenic properties and content of type-C virus particles of a series of lymphomas induced by radiation leukemia virus (RadLV) in Wistar Furth (W/Fu) inbred rats. In conformity with previous studies, adult syngeneic rats ordinarily reject these tumors unless these recipients are irradiated. Evidence indicates that this rejection involves an immunologic mechanism elicited by a new transplantation antigen shared by different RadLV-induced lymphomas of W/Fu rats. All lymphomas rejected by adult syngeneic hosts had high concentrations of the RadLV cell-surface antigen, as revealed by in vitro cytotoxic and absorption tests. The concentration of this antigen was lower in a few tumors able to grow in nonirradiated adult hosts. Electron microscopy of leukemic tissues and plasma of rats with either primary or transplanted syngeneic lymphomas showed type-C virus particles in concentrations markedly higher than those previously observed in RadLV-induced lymphomas of mice. Progressive growth of 3 RadLV-induced lymphomas in rats preimmunized with the same tumor occasionally was observed. In contrast to the original lymphoma lines, sublines isolated from these outgrowths could be maintained by serial transplantation in nonirradiated adult W/Fu rats, and they were not susceptible to the rejection response of specifically preimmunized rats. They were also fully resistant to the specific cytotoxicity of RadLV antisera. After serial passage in nonirradiated recipients, in vitro absorption experiments indicated an apparently complete loss of the RadLV antigen. Extensive electron microscopic examination of the RadLV lymphoma sublines indicated that virus particles were either absent or radically decreased in concentration as compared to the original lines. One of these sublines, tested after 3 consecutive passages in preirradiated hosts, had no restoration of the antigen.
Fate of Recirculating B16 Melanoma Metastatic Variant Cells in Parabiotic Syngeneic Recipients: Brief Communication 2
Authors: Isaiah J. Fidler, Garth L. Nicolson
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Fate of Recirculating B16 Melanoma Metastatic Variant Cells in Parabiotic Syngeneic Recipients: Brief Communication Get access Isaiah J. Fidler, Isaiah J. Fidler Search for other works by this author on: Oxford Academic PubMed Google Scholar Garth L. Nicolson Garth L. Nicolson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 6, June 1977, Pages 1867–1872, https://doi.org/10.1093/jnci/58.6.1867 Published: 01 June 1977 Article history Received: 29 October 1976 Accepted: 30 December 1976 Published: 01 June 1977
Estrogen Receptor Status by Immunohistochemistry Is Superior to the Ligand-Binding Assay for Predicting Response to Adjuvant Endocrine Therapy in Breast Cancer
Authors: Jennet M. Harvey, Gary M. Clark, C. Kent Osborne, D. Craig Allred
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Immunohistochemistry (IHC) is a newer technique for assessing the estrogen receptor (ER) status of breast cancers, with the potential to overcome many of the shortcomings associated with the traditional ligand-binding assay (LBA). The purpose of this study was to evaluate the ability of ER status determination by IHC, compared with LBA, to predict clinical outcome—especially response to adjuvant endocrine therapy—in a large number of patients with long-term clinical follow-up. PATIENTS AND METHODS: ER status was evaluated in 1,982 primary breast cancers by IHC on formalin-fixed paraffin-embedded tissue sections, using antibody 6F11 and standard methodology. Slides were scored on a scale representing the estimated proportion and intensity of positive-staining tumor cells (range, 0 to 8). Results were compared with ER values obtained by the LBA in the same tumors and to clinical outcome. RESULTS: An IHC score of greater than 2 (corresponding to as few as 1% to 10% weakly positive cells) was used to define ER positivity on the basis of a univariate cut-point analysis of all possible scores and disease-free survival (DFS) in patients receiving any adjuvant endocrine therapy. Using this definition, 71% of all tumors were determined to be ER-positive by IHC, and the level of agreement with the LBA was 86%. In multivariate analyses of patients receiving adjuvant endocrine therapy alone, ER status determined by IHC was better than that determined by the LBA at predicting improved DFS (hazard ratios/P = 0.474/.0008 and 0.707/.3214, respectively) and equivalent at predicting overall survival (0.379/.0001 and 0.381/.0003, respectively). CONCLUSION: IHC is superior to the LBA for assessing ER status in primary breast cancer because it is easier, safer, and less expensive, and has an equivalent or better ability to predict response to adjuvant endocrine therapy.