tbuckley/cabot-search huggingface dataset:
Experience of weekly paclitaxel therapy in patients with metastatic breast cancer at a single cancer institution
Authors: Y. J. Summers, G. Mullin, A. Clayton, A. Armstrong, G. Wilson, A. M. Wardley
Journal: Journal of Clinical Oncology (2005)

855 Background: Paclitaxel is an active agent for the treatment of metastatic breast cancer (MBC) and is commonly administered on a three weekly schedule. However, this regimen is associated with toxicity, in particular, neuropathy and myelotoxicity, which can make it difficult for patients of poorer performance to tolerate. There are emerging data indicating that weekly administration is both better tolerated and may be more efficacious. Methods: We performed a retrospective case note review of all patients with MBC treated weekly paclitaxel (WP) at a single institution, the Christie Hospital, Manchester, from November 2001 to June 2004. Results: 43 patients with MBC received WP; 32 receiving WP alone and 11 patients also received concurrent trastuzumab (WP+T). WP was given as first line therapy for MBC in 58% patients. The median age of the patients receiving WP alone was 59.5yrs; 53% with WHO PS 2–4. Those also receiving WP+T were younger (median age 52yrs) with better PS (18% PS 2–4). Patients on WP alone received a median of 10 weeks treatment; those receiving WP+T received a median of 17 weeks paclitaxel. Only 5 patients (16%) receiving WP alone had grade 3 or 4 neutropenia, and 3 patients (9%) had an episode of febrile neutropenia. In the WP+T patients, there was no grade 3 or 4 neutropenia, however, 27% of patients experienced grade 3 neuropathy. Grade 3 lethargy occurred in 6 patients (14%). Overall, 9 of 43 patients achieved a partial response (PR 21%), 15 had stable disease (SD 35%). 8 of 11 (72%) of the patients receiving WP+T achieved SD or better. The median time to progression was 133 days and 191 days in the WP alone and WP+T groups respectively. The median overall survival is 289 days in the WP alone group, and has not yet been reached in the WP+T group. Survival was not significantly associated with performance status. Conclusions: In keeping with recently published literature, we have found weekly paclitaxel to be an effective and well tolerated regimen for patients with MBC including those with poor performance status. No significant financial relationships to disclose.
Promotion of 2-(Ethylnitrosamino)ethanol-Induced Renal Carcinogenesis in Rats by Nephrotoxic Compounds: Positive Responses With Folic Acid, Basic Lead Acetate, and &lt;italic&gt;N&lt;/italic&gt;-(3,5-Dichlorophenyl)succinimide But Not With 2,3-Dibromo-1-propanol Phosphate&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: T Shirai, M Ohshima, A Masuda, S Tamano, N Ito
Journal: JNCI Journal of the National Cancer Institute (1984)

The promoting effects of nephrotoxic chemicals, folic acid (FA), N-(3,5-dichlorophenyl)succinimide (NDPS), 2,3-dibromo-1-propanol phosphate (Tris-BP), and basic lead acetate (LAB), on 2-(ethylnitrosamino)ethanol (EHEN)-induced renal carcinogenesis were examined in F344 rats. The rats were treated with 0.1% EHEN in their drinking water for 1 week and then given one of the nephrotoxic chemicals for 35 weeks. FA was injected sc once a week at a dose of 300 mg/kg for the first 8 weeks and thereafter at 100 mg/kg. NDPS, Tris-BP, and LAB were mixed in the diet at concentrations of 0.5, 0.01, and 0.1%, respectively. At week 3 the right kidney was removed to enhance renal neoplasia. Renal cell tumor incidence was significantly increased by both FA and LAB and was slightly increased by NDPS, whereas Tris-BP had no effect. The data show that FA, LAB, and NDPS are promoters of EHEN-induced renal carcinogenesis.
In vivo real-time assessment of colorectal polyp histology using an optical biopsy forceps system based on laser-induced fluorescence spectroscopy
Authors: Timo Rath, Gian Tontini, Michael Vieth, Andreas Nägel, Markus Neurath, Helmut Neumann
Journal: Endoscopy (2016)

<b>Background and study aims:</b> In order to reduce time, costs, and risks associated with resection of diminutive colorectal polyps, the American Society for Gastrointestinal Endoscopy (ASGE) recently proposed performance thresholds that new technologies should meet for the accurate real-time assessment of histology of colorectal polyps. In this study, we prospectively assessed whether laser-induced fluorescence spectroscopy (LIFS), using the new WavSTAT4 optical biopsy system, can meet the ASGE criteria. <b>Patients and methods:</b> 27 patients undergoing screening or surveillance colonoscopy were included. The histology of 137 diminutive colorectal polyps was predicted in real time using LIFS and findings were compared with the results of conventional histopathological examination. The accuracy of predicting polyp histology with WavSTAT4 was assessed according to the ASGE criteria. <b>Results:</b> The overall accuracy of LIFS using WavSTAT4 for predicting polyp histology was 84.7 % with sensitivity, specificity, and negative predictive value (NPV) of 81.8 %, 85.2 %, and 96.1 %. When only distal colorectal diminutive polyps were considered, the NPV for excluding adenomatous histology increased to 100 % (accuracy 82.4 %, sensitivity 100 %, specificity 80.6 %). On-site, LIFS correctly predicted the recommended surveillance intervals with an accuracy of 88.9 % (24/27 patients) when compared with histology-based United States guideline recommendations; in the 3 patients for whom LIFS- and histopathology-based recommended surveillance intervals differed, LIFS predicted shorter surveillance intervals. <b>Conclusions:</b> From the data of this pilot study, LIFS using the WavSTAT4 system appears accurate enough to allow distal colorectal polyps to be left in place and nearly reaches the threshold to “resect and discard” them without pathologic assessment. WavSTAT4 therefore has the potential to reduce costs and risks associated with the removal of diminutive colorectal polyps.
Trimodality treatment of early stage Malignant Pleural Mesothelioma (MPM): a single institutional experience
Authors: Elke Vandenbroucke, Marleen Praet, Karim Vermaelen, Veerle Surmont, Frederic De Ryck, Kurt Tournoy, Robert Gosselin, Wilfried De Neve, Frank Vermassen, Jan Van Meerbeeck
Journal: Journal of Thoracic Oncology (2009)
Antigens Associated With Acute Leukemia Detected in the Primed Lymphocyte Test 2
Authors: Nancy L. Reinsmoen, John H. Kersey, Edmond J. Kersey
Journal: JNCI Journal of the National Cancer Institute (1978)

Mixed lymphocyte culture (MLC) studies of families with several leukemia patients, all potential bone marrow transplant recipients, demonstrated that cells from acute myelogenous leukemia patients (5 of 5) and acute undifferentiated leukemia patients (1 of 4) in relapse stimulated autologous lymphocytes as well as lymphocytes from siblings known to be identical at the major histocompatibility linkage group. In the patients studied, the blast transformation induced by leukemia cells was not detectable when the patient was in remission. Stimulation by leukemia cells also elicited increased responses of the lymphocytes from normal haploidentical siblings, parents, and unrelated individuals as compared to stimulation by normal allogeneic cells or leukemia cells of patients with leukemia in remission. The primed lymphocyte test (PLT) was used successfully to establish HLA-D identity of the leukemia patients and their respective HLA-identical siblings, despite high percentages of circulatory blasts. Utilizing lymphocytes from normal siblings primed against the leukocytes from an HLA-identical sibling with leukemia, we also presented results of PLT's which suggested that the stimulation induced by leukemia cells in MLC was produced by leukemia-associated antigens.
In Vitro Growth of Lucké Renal Tumor Cells2
Authors: Joseph Zambernard
Journal: JNCI Journal of the National Cancer Institute (1973)

Although primary cultures of Lucké renal tumor cells were readily established in vitro, it was not possible to subculture these cells until now. Three Lucké tumors were established in vitro; 1 was subcultured through 10 generations. This success was attributed to the use of highly purified trypsin for dissociating primary tumor cells and subsequent confluent cell monolayers.
Darwinian Dynamics of Intratumoral Heterogeneity: Not Solely Random Mutations but Also Variable Environmental Selection Forces
Authors: Mark C. Lloyd, Jessica J. Cunningham, Marilyn M. Bui, Robert J. Gillies, Joel S. Brown, Robert A. Gatenby
Journal: Cancer Research (2016)

Spatial heterogeneity in tumors is generally thought to result from branching clonal evolution driven by random mutations that accumulate during tumor development. However, this concept rests on the implicit assumption that cancer cells never evolve to a fitness maximum because they can always acquire mutations that increase proliferative capacity. In this study, we investigated the validity of this assumption. Using evolutionary game theory, we demonstrate that local cancer cell populations will rapidly converge to the fittest phenotype given a stable environment. In such settings, cellular spatial heterogeneity in a tumor will be largely governed by regional variations in environmental conditions, for example, alterations in blood flow. Model simulations specifically predict a common spatial pattern in which cancer cells at the tumor-host interface exhibit invasion-promoting, rapidly proliferating phenotypic properties, whereas cells in the tumor core maximize their population density by promoting supportive tissue infrastructures, for example, to promote angiogenesis. We tested model predictions through detailed quantitative image analysis of phenotypic spatial distribution in histologic sections of 10 patients with stage 2 invasive breast cancers. CAIX, GLUT1, and Ki67 were upregulated in the tumor edge, consistent with an acid-producing invasive, proliferative phenotype. Cells in the tumor core were 20% denser than the edge, exhibiting upregulation of CAXII, HIF-1Î±, and cleaved caspase-3, consistent with a more static and less proliferative phenotype. Similarly, vascularity was consistently lower in the tumor center compared with the tumor edges. Lymphocytic immune responses to tumor antigens also trended to higher level in the tumor edge, although this effect did not reach statistical significance. Like invasive species in nature, cancer cells at the leading edge of the tumor possess a different phenotype from cells in the tumor core. Our results suggest that at least some of the molecular heterogeneity in cancer cells in tumors is governed by predictable regional variations in environmental selection forces, arguing against the assumption that cancer cells can evolve toward a local fitness maximum by random accumulation of mutations. Cancer Res; 76(11); 3136-44. ©2016 AACR.
Biomedical Research Enters the Steady State
Authors: Harold Varmus
Journal: New England Journal of Medicine (1995)

Two and a half years ago, when I was still a private citizen working at the University of California, San Francisco, my colleagues, Mike Bishop and Marc Kirschner, and I offered advice to our new President in Science magazine.1 The first of our 11 recommendations was to increase funding for the National Institutes of Health (NIH) by 15 percent per year, in order to double the NIH budget in five years and restore the success rate for grant applications to at least 30 percent. A year later, just after I had been called to Washington to work for that President . . .
Abstract 11497: Determinants of Changes in Right Ventricular Dimensions and Function Following ST-Segment Elevation Myocardial Infarction
Authors: Georgette E Hoogslag, Marlieke L Haeck, Matthijs A Velders, Helen Boden, Martin J Schalij, Hubert W Vliegen, Jeroen J Bax, Nina Ajmone Marsan, Victoria Delgado
Journal: Circulation (2012)

Introduction: RV function is an important prognostic marker of morbidity and mortality in STEMI patients. However, little is known of the time course of RV function and dimensions, the inter-ventri...
Voriconazole-induced QT-corrected (QTc) interval prolongation, bradycardia, hypothermia, mydriasis in an immunosuppressed patient with Ewing
Authors: S. Alkhallaf, H. Cornille, B. Markowska, Z. Lankri, N. Delepine
Journal: Journal of Clinical Oncology (2009)

e20738 Background: Invasive aspergillosis is an important cause of increased mortality and morbidity in immunocompromised patients. Early treatment of probable aspergillosis by voriconazole is recommended by many authors. Nevertheless direct possible lethal complications must be taken into account. Methods: we describe a case of voriconazole adverse events in a 18 y old patient treated for aplasia by antibiotics and caspofungin. He remained febrile: Voriconazole initiated for digestive mycosis, caugh, endemic aspergillosis. Second injection was badly tolerated ( fever 40 °, dyspnea, chills, myalgias, hypotension) leading to stop Voriconazole. Few hours later, bradycardia (36 bpm/mn), QT c interval prolongation (QTc 482ms), bilateral mydriasis, hypothermia appeared. Others risks for cardiac events were studied: prior cardiotoxic chemotherapy; lightly low calcemia and magnesemia, negative T ondes, traducing major potassium deficit in cardiac cells, in spite of initially normal kaliemia (4.6 mmol/l) mild hypokalemia (3.3 meq/l). Systemic infection was eliminated, cerebral MRI normal, blood dosage of voriconazole at 80 h and 96 h after last dose negative. We discontinued potentially arrhythmogenic drugs. Specific treatment consisted of electrolyte disturbances correction, IV atropine, scopolamine patch. 24 h holter ECG revealed neither torsades de pointes nor ventricular tachycardia. QT c interval remained longer for 3 days. Onde T was normalised at day 6, with disappearance of bradycardia and hypothermia,without any cardiac event. Results: Azole family antifungal agents were pointed out as arrhythmogenic (QTc prolongation, torsades de pointes) in combination or alone. Few data reported bradycardia and QT c prolongation with voriconazole, although the drug package insert warns about such reactions. Furthermore, none case of mydriasis was reported but noted in Pfizer American data file(&lt; 2% of case). Conclusions: Careful monitoring of QTc prolongation and bradycardia in patients receiving voriconazole is mandatory, particularly those with electrolyte disturbances, concomitant QT prolonging drugs, and /or receiving toxic cardiac chemotherapy. No significant financial relationships to disclose.
Standardization of allergen products: 3. Validation of candidate European Pharmacopoeia standard methods for quantification of major birch allergen Bet v 1
Authors: S. Kaul, J. Zimmer, O. Dehus, A. Costanzo, A. Daas, K. H. Buchheit, J. A. Asturias, D. Barber, J. Carnés, M. Chapman, J. Dayan‐Kenigsberg, S. Döring, F. Führer, K. M. Hanschmann, T. Holzhauser, A. Ledesma, P. Moingeon, E. Nony, C. Pini, G. Plunkett, G. Reese, E. Sandberg, I. Sander, D. Strecker, C. Valerio, R. van Ree, S. Vieths
Journal: Allergy (2016)

The BSP090 project aims at establishing European Pharmacopoeia Reference Substances in combination with the corresponding ELISA methods for the quantification of major allergens in allergen products. Two sandwich ELISAs proved suitable for quantification of Bet v 1, the major birch pollen allergen, in preceding phases of BSP090.Two Bet v 1-specific ELISA systems were compared with respect to accuracy and precision in a ring trial including 13 laboratories. Model samples containing recombinant rBet v 1.0101 as well as native birch pollen extracts were measured independently at least three times in each facility. The assessment was completed with a comparative quantification of Bet v 1 in 30 marketed birch allergen products in one laboratory, simulating the future use as reference method.In the collaborative study, both candidate ELISAs confirmed their suitability to quantify recombinant and native Bet v 1. ELISA-A showed higher precision and lower interlaboratory variability, yet ELISA-B exhibited slightly higher accuracy. Subsequent parallel measurement of Bet v 1 in a panel of 'real-life' birch allergen products indicated better repeatability of ELISA-B. Both systems detected substantial differences in Bet v 1 content between allergen products, but the effect was more pronounced using ELISA-B due to persistently higher values compared to ELISA-A.In the collaborative study, no deciding differences were observed between the two candidate ELISAs. Further comparison under conditions simulating the intended use combined with the criterion of long-term availability enabled the selection of one Bet v 1-specific ELISA for proposal as European Pharmacopoeia standard method.
Interaction of Dietary Fat and Protein on Pancreatic Carcinogenesis in Syrian Golden Hamsters&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: D F Birt, K R Stepan, P M Pour
Journal: JNCI Journal of the National Cancer Institute (1983)

The role of interactions between dietary fat and protein in experimental pancreatic cancer was determined in Syrian golden hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Two levels of corn oil [4.5 and 18 g/385 kilocalorie (kcal)] were fed with each of two levels of casein (9 g/385 kcal and 36 g/385 kcal), either before or after a single sc injection of BOP (10 mg/kg body wt) at 8 weeks of age. Control diet was fed at other times (9 g corn oil and 18 g casein/385 kcal). The pancreatic ductular carcinoma incidence and multiplicity (average No. of tumors/tumor-bearing animals) increased as dietary fat and protein levels rose in hamsters fed the four diets after carcinogen treatment. Enhanced carcinogenesis by high-fat (HF) diets occurred only in hamsters fed the high-protein (HP) level, and protein effects were seen only with the HF diets. The low-fat-low-protein (LF-LP) diet inhibited pancreatic carcinogenesis among the hamsters given the four diets before BOP treatment. Pancreatic adenoma yields were elevated in hamsters given either HF or HP diets following BOP treatment, by comparison with the low levels. However, when diets were fed before BOP treatment, an increased yield occurred with the rise in protein, but the yield was reduced in males with the increase in fat. Acinar cell nodules were observed primarily in hamsters fed LP levels after BOP, and their multiplicity was highest in those given the HF diet. The interaction between dietary fat and protein demonstrated the interdependence of the effects of these two nutrients on pancreatic carcinogenesis in hamsters.
Barriers to Clinical Trial Participation as Perceived by Oncologists and Patients
Authors: Neal J. Meropol, Joanne S. Buzaglo, Jennifer Millard, Nevena Damjanov, Suzanne M. Miller, Caroline Ridgway, Eric A. Ross, John D. Sprandio, Perry Watts
Journal: Journal of the National Comprehensive Cancer Network (2007)

Although clinical trial research is required for the development of improved treatment strategies, very few cancer patients participate in these studies. The purpose of this study was to describe psychosocial barriers to clinical trial participation among oncologists and their cancer patients. A survey was distributed to all medical oncologists in Pennsylvania and a subset of their patients. Relevant background information and assessment of practical and psychosocial barriers to clinical trial participation were assessed. Among 137 oncologists and 170 patients who completed the surveys, 84% of patients were aware of clinical trials, and oncologists and patients generally agreed that clinical trials are important to improving cancer treatment. However, oncologists and patients were more likely to consider clinical trials in advanced or refractory disease. When considering 7 potential barriers to clinical trials, random assignment and fear of receiving a placebo were ranked highly by both patients and oncologists. Patients identified fear of side effects as the greatest barrier to clinical trial participation, whereas oncologists ranked this psychosocial barrier as least important to their patients. Overall, the study found that although oncologists and patients are aware of clinical trials and have favorable attitudes toward them, psychosocial barriers exist for patients that may impact participation in clinical trials. Furthermore, important discrepancies exist between the perceptions of oncologists and those of patients regarding what the psychosocial barriers are. We concluded that characterizing oncologist and patient perceived barriers can help improve communication and decision making about clinical trials, such that participation may be optimized.
Phase I/II trial of pegylated arginine deiminase (ADI-PEG20) in unresectable hepatocellular carcinoma
Authors: K. A. Delman, T. D. Brown, M. Thomas, C. M. Ensor, F. W. Holtsberg, J. S. Bomalaski, M. A. Clark, S. A. Curley
Journal: Journal of Clinical Oncology (2005)

4139 Background: Over 1 million new cases of hepatocellular cancer (HCC) occur annually with most patients dying within six months of diagnosis. Less than 10% of patients are candidates for resection or transplantation so other effective therapies must be developed. It was recently noted that HCC cell lines require exogenous arginine for growth and we reported the efficacy of arginine deiminase, an arginine-degrading enzyme covalently attached to polyethylene glycol, in inducing regression of HCC in a single patient. This study examines the efficacy of this agent in a cohort of 35 patients in a combined phase I/II study. Methods: ADI-PEG20 was administered by weekly intramuscular injection to eligible patients under guidelines of an IRB-approved protocol. The phase I component consisted of an escalating dose of ADI-PEG20 to an optimal biologic dose (OBD) of 160 IU/m2; with the OBD defined as the dose that reduced plasma arginine levels to < 2 μM. The phase II arm utilized the OBD for initial dosing regimen but allowed patients to receive a higher dose of 240 IU/m2. Patients were followed clinically and radiographically to assess toxicity and to follow disease status. Results: Of 35 patients enrolled, 1 became resectable, 2 had stable disease, 4 did not complete the study (2 for allergic reactions, 2 for intercurrent illnesses) and 28 progressed with a mean duration before progression of 3.4 months (range, 1 to 13 months). All patients achieved arginine levels < 2 μM. The patient who underwent resection died postoperatively from portal vein thrombosis leading to liver failure. Although radiologic evaluation showed stable disease in this patient, pathology demonstrated minimal viable tumor. There were no deaths on study but 3 patients died within 30 days of their last dose of ADI-PEG. All patients had at least grade I laboratory abnormalities while 12 had grade III (6 liver function, 2 electrolyte, 2 anemias, 1 fever and 1 elevated lipase) and 3 had grade IV toxicities (2 liver function abnormalities, 1 elevated lipase). Conclusions: ADI-PEG 20 is a potentially useful and safe agent in unresectable or advanced HCC. Based on results of the phase I/II study, phase II studies combining ADI-PEG 20 with cytotoxic agents are being developed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Phoenix Pharmacologics