tbuckley/cabot-search huggingface dataset:
Alpha-fetoprotein radioimmunoassay in blood diseases. (Letter)
Authors: Masseyeff R, Cassuto Jp, Krebs Bp, Audoly P, Dujardin P
Journal: New England Journal of Medicine (1974)

Using the radioimmunoassay method routinely used in our laboratory and already described we have measured the serum levels of alpha-fetoprotein (AFP) in adults suffering from the following blood dyserasias;  acute myeloid leukemia eight cases;  acute lymphoid leukemia five;  chronic lymphocytic leukemia and lymphosarcoma six;  chronic myeloid leukemia four;  reticulosarcoma two;  myelomatosis two;  Hodgkins disease four;  Waldenstroms disease one;  Biermers disease three;  hemoglobinosis C one;  thymoma one;  ostcomyclosclerosis three;  idiopathic bone-marrow aplasia four;  and infectious mononucleosis six.  We excluded children since previous studies showed that a rise in serum AFP may be more easily induced in children than in adults.  In 49 of 50 cases the AFP levels fell within the normal adult range between 0.1 and 5.8 ng p/ml (mean 2.6 ng per milliliter S.D. 1.6) thus confirming the observations of Abelev et al. who used the immunoradioantographic method in a series of 42 patients with blood diseases.  The 12 positive cases (the nature of which was not specified) obtained with use of the aggregate hemagglutination procedure are difficult to interpret in view of the fact that this method as mentioned by the authors also gives false-positive results.  Dufour suggested that the hemopoietic cells of the embryonic liver were involved in AFP production.  On this basis raised levels of serum AFP might have been anticipated in the blood diseases of the adult in which myelopoiesis recurred in the liver and especially in our three patients with osteomyelosclerosis.  Serum levels did not rise indicating that if hemopoietic cells of the fetal liver do form AFP the context is different from that of recurrent myclopoiesis in an adult liver.  The finding of a moderately elevated level of AFP (50 ng /ml in only one of the six cases of infectious mononucleosis observed in a 16-year-old boy is of interest since it is known that in this disease the liver may be transitorily involved in 80 percent of patients.  This positive AFP result suggests that on occasion the serum AFP may rise in infectious mononucleosis as it may in viral hepatitis.  (FULL-TEXT)
HGS-ETR2—A fully human monoclonal antibody to TRAIL-R2: Results of a phase I trial in patients with advanced solid tumors
Authors: A. Patnaik, H. Wakelee, M. Mita, A. Fitzgerald, M. Hill, N. Fox, T. Howard, S. Ullrich, A. Tolcher, B. Sikic
Journal: Journal of Clinical Oncology (2006)

3012 Background: HGS-ETR2 is a fully-human high-affinity monoclonal antibody that is agonistic to the Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor 2 (TRAIL-R2, DR5). TRAIL-R2 is expressed more widely on the surface of tumor cells than normal cells; binding of HGS-ETR2 to TRAIL-R2 leads to activation of the extrinsic apoptosis pathway. HGS-ETR2 shows anti-tumor activity at doses ≥ 0.3 mg/kg in xenograft models, both as a single agent and in combination with chemotherapeutic agents. Methods: This phase 1, dose-escalation study assessed the safety, tolerability, pharmacokinetics and immunogenicity of HGS-ETR2 administered IV every 14 days in patients with advanced solid tumors. Patients received HGS-ETR2 until disease progression or unacceptable toxicity. Tumor measurements were repeated every 2 months. Results: To date, 31 patients have received 167 courses of HGS-ETR2 over 5 dose levels: 0.1, 0.3, 1.0, 3.0 and 10.0 mg/kg q14 days. The majority (26 of 31) received at least 4 courses. One patient experienced a dose-limiting toxicity of grade 3 hyperamylasemia at the 10 mg/kg dose level. The event was determined to be possibly related to HGS-ETR2 and also possibly related to a nutritional supplement. Stable disease was achieved in 10 patients for 4 to 16 cycles. One patient with chemotherapy-refractive Hodgkin’s disease had a tumor regression of abdominal disease. HGS-ETR2 pharmacokinetics were linear up to 10 mg/kg. At the 10 mg/kg dose, the pharmacokinetics were characterized by a mean (SD) t 1/2β of 11 (4) days, CL of 6.0 (0.7) mL/day, and V 1 of 47 (8) mL/kg, slightly larger than the plasma volume. The 1.8-fold larger V ss of 85 (27) mL/kg indicates that HGS-ETR2 distributes outside the plasma compartment. Human anti-human antibody formation has not been detected. Conclusions: HGS-ETR2 can be safely administered every 14 days at doses up to and including 10 mg/kg. Further evaluation of HGS-ETR2 is planned, including studies of HGS-ETR2 in combination with chemotherapeutic agents. [Table: see text]
Prospective, Interdisciplinary Randomized Clinical Trials for Patients With Cancer in the Emergency Department
Authors: Charles R. Thomas
Journal: JAMA Oncology (2016)

Corita R. Grudzen, MD, MSHS; Lynne D. Richardson, MD; Pauline N. Johnson, BS; Ming Hu, PhD; Binhuan Wang, PhD; Joanna M. Ortiz, BA; Emmett A. Kistler, MD; Angela Chen, MD; R. Sean Morrison, MD
Feature of Mechanical Left Ventricular Dyssynchrony in Heart Failure Patients with "Very" Narrow QRS Duration: Using Three-dimensional Speckle-tracking Study.
Authors: Kazuhiro Tatsumi, Hidekazu Tanaka, K Matsumoto, Takuma Sawa, Yasuhide Mochizuki, Yoshiki Motoji, Junichi Imanishi, Tatsuya Miyoshi, Mana Hiraishi, Akihiro Kaneko, Keiko Ryo-Koriyama, Yuko Fukuda, Akihiro Yoshida, Hiroya Kawai, Ken-Ichi Hirata
Journal: Circulation (2012)
The clinical significance of triple-negative breast cancer in men (MBC).
Authors: R. Foerster, F. G. Foerster, V. Wulff, B. Schubotz, R. Lange, J. Habeck, D. Baaske, C. Rudlowski
Journal: Journal of Clinical Oncology (2010)

e21011 Background: MBC is an infrequent, but commonly hormone receptor (HR) positive disease. Reports on the expression of the HER2 receptors are contradictory. Therefore the question is raised for the presence of the triple negative phenotype in MBC as well as for its potential prognostic relevance compared to female breast cancer. Methods: Within the scope of a retrospective cohort study within the years 1995-2009 patients' characteristics of 127 MBC (median age: 68 years) were registered in the administrative district of Chemnitz, State of Saxony, Germany. In 104 (81.8%) patients (pts) the HR (progesterone & estrogen receptors) and in 91 (71.6%) pts the HER2 receptor was analyzed by immunohistochemistry or FISH. To compare MBC patients outcome with female breast cancer, 108 matched pairs were created using tumor size, nodal state, metastasis, grading, HR, HER2 as matching criteria. Statistics were performed using SPSS for Windows version 17.0. Results: Overall 91 (87.5%) pts were HR positive. 84 (80%) had an estrogen receptor (ER) positive and 83 (79.8%) a progesterone receptor (PR) positive status. HER2 overexpression/gene amplification was found in 10 (11%) of the MBC cases. Additionally the following subtypes were identified: 70 pts (76.9%) HR+/Her2-, 8 pts (8.8%) HR+/Her2+, 2 pts (2.2%) HR-/Her2+, 11 pts (12.1%) HR-/Her2-. Men with HR negative tumors showed a trend (p=.055) towards unfavorable survival compared to women. Missing ER as well as PR was associated with a poor prognosis whereas PR in men appeared to be of greater prognostic importance (PR p<.001 vs. ER p=.051). Triple-negative men had a significantly (p<.01) worse prognosis than other subtypes or than triple negative women (p<.05). There were no differences regarding disease-free or overall survival between men and women. Conclusions: In our study group, HR+/HER2- tumors were the predominant subtype in male breast cancer and showed an excellent patients outcome. However, like in females tumors with a triple negative subtype had a worse prognostic outcome. Therefore, new therapeutic options for triple negative breast cancer have to be evaluated also in men. No significant financial relationships to disclose.
Engaging patients and stakeholders in the process of designing a clinical trial and patient education platform.
Authors: Lauren M. Rosati, Sarah Douglas, Roger Leventer, Laurie Singer Sievers, Randall W. Swan, James L. Teesdale, Andrew D. McKnight, Anitra Engebretson, Shereef Elnahal, Amy Hacker-Prietz, Omar Badri, Adeel Yang, Nasser M. Al-Sulaihim, Timothy M. Pawlik, Ilene S. Browner, Dan Laheru, Michael A. Erdek, Claire F. Snyder, Thomas J. Smith, Joseph M. Herman
Journal: Journal of Clinical Oncology (2015)

63 Background: Patient engagement during the initiation, development, and implementation of a study has been shown to improve the ethical nature of research and the appropriateness of treatment methods, and insights into how best to partner with patients are needed. We describe our patient engagement experience in developing a clinical trial for non-metastatic pancreatic cancer (PCA). Methods: A team of patient research partners (PRPs) was consulted to design a multi-institutional study to evaluate the efficacy of chemotherapy, stereotactic body radiation therapy, and early palliative care (EPC) in patients with PCA who are typically ineligible for clinical trials due to advanced age, poor performance status, or preexisting comorbidities. PRPs included patients, caregivers, clinical researchers, patient advocacy organizations, and pharmaceutical companies. A 22-item initial survey on personal interests and a 5-item follow-up survey on study design were anonymously completed after two in-person meetings. Results: Of 15 PRPs involved, 9 completed the initial survey and 10 completed the follow-up survey. PRPs were most interested in improving quality of life (QOL, 89%), care coordination (78%), symptom management (67%), stress/anxiety (56%), and survival (56%). Confidence in the care team, hope, QOL, education and understanding, dignity, and pain management were reported to be the most important factors throughout the cancer experience. The majority (89%) requested that study participants have access to the study protocol and research publications supporting the study design. Because all PRPs suggested that a personal website be used to provide information to study participants and to disseminate the results of the study, an online patient education platform was adopted and customized for patients (and caregivers). Furthermore, integration of EPC into the treatment regimen was unanimously endorsed. Conclusions: Engaging PRPs in the process of designing a clinical trial for PCA appears to be feasible and valuable in identifying the study objectives most important to patients. PRPs conveyed that maintaining a good QOL is essential, and adoption of EPC in these patients should be considered.
Apoptotic effects of the docetaxel→OSI-774 combination in non-small cell lung carcinoma (NSCLC) cells
Authors: T. Kimura, C. M. Mahaffey, B. J. Pryde, P. C. Mack, A. M. Davies, D. R. Gandara, P. H. Gumerlock
Journal: Journal of Clinical Oncology (2004)

7143 Background: The epidermal growth factor receptor (EGFR) has been shown to signal through both the mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) pathways, each of which has been shown to be abnormally activated in NSCLC. OSI-774 (Tarceva) is an EGFR tyrosine kinase inhibitor with anti-cancer activity in clinical trials. Docetaxel (Txt), an antimicrotubule agent, is used extensively in NSCLC. We previously reported that in vitro the sequence of Txt →OSI-774 resulted in the greatest proportion of sub-G1 cells compared to the alternate sequence of OSI-774→Txt (Gumerlock, ASCO 2003). Here we hypothesized that this is an apoptotic response that persists, resulting in long-term differences from these alternate administrations. Methods: The NSCLC cell line Calu1 was used as a model because it is EGFR positive and p53-null like the majority of advanced NSCLC tumors. Cells were treated with single doses of OSI-774 (1μM, 24hrs), Txt (50nM, 18hrs), or in these sequences: OSI-774→Txt→drug-free media for 72hrs or Txt→OSI-774→drug-free media. Cleaved poly-ADP-ribose polymerase (PARP) and Caspase-3 apoptosis marker proteins were assessed by Western blotting. Results: The greatest cell death was observed in the Txt→OSI-774→media sequence, while the cells treated with the OSI-774→Txt→media sequence resumed proliferation by 72hrs post-treatment. Cleaved PARP and Caspase-3 were detected in the sequence of Txt→OSI-774, and with simultaneous treatment, but not in the sequence of OSI-774→Txt. Further, cleaved PARP and Caspase-3 persisted to 72hrs after the Txt→OSI-774 treatment. These data support the previous results on sub-G1 cells, and molecularly demonstrate an apoptotic response. Conclusions: 1) The sequence of Txt→OSI-774 showed the greatest levels of apoptosis in NSCLC cells that persisted to at least 72hrs post-treatment. 2) This effect ocurred in p53-null cells, suggesting a potential role in tumor types with high frequencies of disrupted p53. These data form the basis for an ongoing phase I trial examining two regimens of intermittent EGFR blockade with OSI-774 plus Txt. (CM17101, CA62505, HHMI, Aventis, Genentech) Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Oncology Aventis
Evolution of globin expression in the genus Xenopus (Anura: Pipidae).
Authors: E Bürki, M Fischberg
Journal: Molecular Biology and Evolution (1985)

Comparison of electrophoretic globin phenotypes of 18 different Xenopus taxa reveals four different basic types of banding patterns. Each type includes species that also are similar in their morphological, cytogenetical, and biochemical characteristics. Three of these patterns reflect distinct evolutionary lines, while the fourth may be interpreted as the intersection of two of these lines. The composition of the basic pattern of the highly polyploid species is consistent with an allopolyploid origin of most of these species. The number of distinct globin polypeptides--four in the only extant diploid species, X. tropicalis, and five or more in most of the tetraploid species, including X. laevis--suggests that primordial globin genes had undergone duplication either before or after the tetraploidization event. Finally, the individual globin phenotypes are excellent molecular markers that are of great help in identifying the various species but not the subspecies.
A phase II study of <sup>131</sup>I-MIBG for refractory neuroblastoma
Authors: J. M. Maris, G. Yanik, J. Messina, L. Kersun, R. E. Goldsby, J. Huberty, J. Veatch, P. Brophy, S. C. Cheng, R. E. Hawkins, K. K. Matthay
Journal: Journal of Clinical Oncology (2005)

8504 Purpose: To evaluate the effect of disease sites, prior therapy and dose on response rates and toxicity with 131I-MIBG treatment of children with refractory neuroblastoma. Methods: 151 patients with progressive, refractory or relapsed neuroblastoma, age 2–30 years with normal organ function, were treated in a limited institution Phase II study from 8/30/96 to 10/1/04. Patients with adequate hematopoietic stem cells (HSC) were treated with 18 mCi/kg of 131I-MIBG; those without HSC were treated at 12 mCi/kg. Patients were stratified according to whether or not they had received prior myeloablative therapy (HSCT) and whether or not they had soft tissue (ST) involvement or just bone and/or bone marrow disease (B/BM). Results: Hematologic toxicity was common, with 28% of patients receiving autologous HSC infusion for prolonged myelosuppression. Non-hematological toxicity was rare, with 6% of patients experiencing hepatic, 6% pulmonary, and 12% infectious grade 3–4 toxicity. The overall response rate (CR/VGPR/PR) for 142 evaluable patients was 35%, with response rate by stratum. The response rate for patients with B/BM only was 43% vs. 30% for patients ST lesions (p=0.11). In addition, 52 patients (37%) showed stable disease after treatment, often with improved performance status. With a median follow-up of 6 months (range 0 - 77 months), overall estimated survival was 47% at 1 year and 31% at 2 years. The median survival for stratum 1–4 was 11.7, 12.1, 5.0, and 9.4 months, respectively. There were trends towards increased survival for patients with prior HSCT vs. those with primary refractory disease, and for the group treated at 18 mCi/kg vs. 12 mCi/kg. Conclusions: 131I-MIBG therapy results in a high response rate for resistant neuroblastoma with low hematological toxicity. Efficacy is apparently greater for disease restricted to bone or bone marrow sites, for relapsed compared to primary refractory disease, and for higher doses of 131I-MIBG. No significant financial relationships to disclose.
Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: a population-based surveillance study
Authors: Grant A Mackenzie, Philip C Hill, David J Jeffries, Ilias Hossain, Uchendu Uchendu, David Ameh, Malick Ndiaye, Oyedeji Adeyemi, Jayani Pathirana, Yekini Olatunji, Bade Abatan, Bilquees S Muhammad, Augustin E Fombah, Debasish Saha, Ian Plumb, Aliu Akano, Bernard Ebruke, Readon C Ideh, Bankole Kuti, Peter Githua, Emmanuel Olutunde, Ogochukwu Ofordile, Edward Green, Effua Usuf, Henry Badji, Usman N A Ikumapayi, Ahmad Manjang, Rasheed Salaudeen, E David Nsekpong, Sheikh Jarju, Martin Antonio, Sana Sambou, Lamin Ceesay, Yamundow Lowe-Jallow, Momodou Jasseh, Kim Mulholland, Maria Knoll, Orin S Levine, Stephen R Howie, Richard A Adegbola, Brian M Greenwood, Tumani Corrah
Journal: The Lancet Infectious Diseases (2016)

Little information is available about the effect of pneumococcal conjugate vaccines (PCVs) in low-income countries. We measured the effect of these vaccines on invasive pneumococcal disease in The Gambia where the 7-valent vaccine (PCV7) was introduced in August, 2009, followed by the 13-valent vaccine (PCV13) in May, 2011.We conducted population-based surveillance for invasive pneumococcal disease in individuals aged 2 months and older who were residents of the Basse Health and Demographic Surveillance System (BHDSS) in the Upper River Region, The Gambia, using standardised criteria to identify and investigate patients. Surveillance was done between May, 2008, and December, 2014. We compared the incidence of invasive pneumococcal disease between baseline (May 12, 2008-May 11, 2010) and after the introduction of PCV13 (Jan 1, 2013-Dec 31, 2014), adjusting for changes in case ascertainment over time.We investigated 14 650 patients, in whom we identified 320 cases of invasive pneumococcal disease. Compared with baseline, after the introduction of the PCV programme, the incidence of invasive pneumococcal disease decreased by 55% (95% CI 30-71) in the 2-23 months age group, from 253 to 113 per 100 000 population. This decrease was due to an 82% (95% CI 64-91) reduction in serotypes covered by the PCV13 vaccine. In the 2-4 years age group, the incidence of invasive pneumococcal disease decreased by 56% (95% CI 25-75), from 113 to 49 cases per 100 000, with a 68% (95% CI 39-83) reduction in PCV13 serotypes. The incidence of non-PCV13 serotypes in children aged 2-59 months increased by 47% (-21 to 275) from 28 to 41 per 100 000, with a broad range of serotypes. The incidence of non-pneumococcal bacteraemia varied little over time.The Gambian PCV programme reduced the incidence of invasive pneumococcal disease in children aged 2-59 months by around 55%. Further surveillance is needed to ascertain the maximum effect of the vaccine in the 2-4 years and older age groups, and to monitor serotype replacement. Low-income and middle-income countries that introduce PCV13 can expect substantial reductions in invasive pneumococcal disease.GAVI's Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP), Bill & Melinda Gates Foundation, and the UK Medical Research Council.
Antitumor Activity of the DNA Fraction from &lt;italic&gt;Mycobacterium bovis&lt;/italic&gt; BCG. II. Effects on Various Syngeneic Mouse Tumors&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: S Shimada, O Yano, H Inoue, E Kuramoto, T Fukuda, H Yamamoto, T Kataoka, T Tokunaga
Journal: JNCI Journal of the National Cancer Institute (1985)

MY-1, a fraction extracted from BCG and composed of 70.0% DNA and 28.0% RNA, was examined for its antitumor activity against 9 different syngeneic mouse tumors. Tumor regression was induced in almost all of the mice bearing any of five kinds of solid tumors by repeated intralesional injections of 100 micrograms MY-1. When cells of some tumors were inoculated intradermally together with MY-1, tumor growth was suppressed, lung metastases were inhibited, and the survival times of mice bearing 1 of 3 leukemic tumors were prolonged. Repeated sc injections with MY-1 in sites remote from tumor cell inoculation or repeated iv injections were more or less effective against three kinds of solid tumors. Mice inoculated with Lewis lung carcinoma cells in a hind footpad and whose legs were amputated 9 days later were given iv or sc injections of MY-1 every other day (8 times in total), resulting in substantial prolongation of survival. No direct cytotoxicity of MY-1 for these tumors could be shown in three kinds of experiments, which indicates that the antitumor mechanism of MY-1 is host mediated. MY-1 was equally effective in mice with or without presensitization with BCG, whereas BCG was much more effective in BCG-sensitized mice. This finding suggests that a delayed-type hypersensitivity reaction elicited by BCG protein is not required for the antitumor activity of MY-1.
Association of temporary blood pressure drop after bevacizumab administration with clinical course of advanced colorectal cancer.
Authors: Masashi Kanai, Hiroshi Ishiguro, Yukiko Mori, Toshiyuki Kitano, Takafumi Nishimura, Shigemi Matsumoto, Kazuhiro Yanagihara, Tsutomu Chiba, Masakazu Toi
Journal: Journal of Clinical Oncology (2012)

528 Background: Hypertension is a common adverse event of bevacizumab and recent data demonstrates that this event is associated with a better clinical course. However, a blood pressure drop after bevacizumab administration and its clinical significance have not yet been reported. Methods: Between August 2007 and October 2010, 85 patients with colorectal cancer underwent palliative chemotherapy using bevacizumab at Kyoto University Hospital. For these patients, we obtained data using both the designated database system (CyberOncology, CyberLaboratory Co. Ltd., Ibaragi, Japan) and the hospital’s electronic medical records system on blood pressure values at 0 min (before administration), at 90 min and 180 min after the initiation of bevacizumab during the first three cycles of bevacizumab treatment. Out of the 85 patients, there were 81 for whom two or more sets of blood pressure data from the first three cycles were available. Therefore, we retrieved data from a total of 162 bevacizumab administrations in 81 patients (data from 2 separate administrations per patient). Results: Twenty-five patients (30%) demonstrated an average temporary drop of 20 mm Hg or more in systolic blood pressure between 0 and 90 min. We classified these 25 patients as group A and the others as group B. In group A the mean blood pressure drop between 0 and 90 min was 25 and 30 mm Hg in the first and second monitoring, respectively, compared with 3 and 5 mm Hg in group B. There were no significant differences between the 2 groups in their baseline characteristics. Interestingly, median time to treatment failure (TTF) was significantly longer in group A compared to group B (291 vs. 162 days; hazard ratio, 0.53; 95% CI, 0.31 – 0.89; P = 0.02). Furthermore, the proportion of patients who required intervention with antihypertensive drugs during bevacizumab treatment was significantly higher in group A compared to group B (36% vs 4%; P &lt; 0.01). Conclusions: Our current study suggests that a temporary blood pressure drop after bevacizumab administration could be a predictive marker for bevacizumab treatment.