tbuckley/cabot-search huggingface dataset:
Six Months of Maintenance Chemotherapy After Intensified Treatment for Acute Lymphoblastic Leukemia of Childhood
Authors: Yasunori Toyoda, Atsushi Manabe, Masahiro Tsuchida, Ryohji Hanada, Koichiro Ikuta, Yuri Okimoto, Akira Ohara, Yohji Ohkawa, Taijiroh Mori, Kohichi Ishimoto, Takeyuki Sato, Takashi Kaneko, Miho Maeda, Ken-ichi Koike, Toshiji Shitara, Yasutaka Hoshi, Ryohta Hosoya, Yukiko Tsunematsu, Fumio Bessho, Shinpei Nakazawa, Tomohiro Saito
Journal: Journal of Clinical Oncology (2000)

We postulated that intensification of chemotherapy immediately after remission induction might reduce the leukemic cell burden sufficiently to allow an abbreviated period of antimetabolite therapy.Three hundred forty-seven children (ages 1 to 15 years) with previously untreated acute lymphoblastic leukemia (ALL) were enrolled onto the Tokyo L92-13 study, which excluded patients with mature B-cell ALL and patients less than 1 year old. One hundred twenty-four patients were classified as standard risk, 122 as high risk, and 101 as extremely high risk, according to age, peripheral-blood leukocyte count, selected genetic abnormalities, and immunophenotype. All subjects received four drugs for remission induction, followed by a risk-directed multidrug intensification phase and therapy for presymptomatic leukemia in the CNS. Maintenance chemotherapy with oral mercaptopurine and methotrexate was administered for 6 months, with all treatment stopped by 1 year after diagnosis.The mean (+/- SD) event-free survival (EFS) and overall survival rates for all patients were 59.5% +/- 3.4% and 81.5% +/- 2.2%, respectively, at 5. 5 years after diagnosis. EFS rates by risk category were similar (60. 2% +/- 6.0% for standard risk, 57.7% +/- 5.6% for high risk, and 62. 5% +/- 5.7% for extremely high risk), whereas overall survival rates differed significantly (91.2% +/- 2.7%, 80.0% +/- 4.1%, and 72.1% +/- 4.5%, respectively, P <.0001 by the log-rank test). There were 107 relapses. Eighty-five (79.4%) of these 107 patients achieved second complete remissions, with subsequent EFS rates of 61.5% +/- 7. 9% (standard risk), 42.6% +/- 8.1% (high risk), and 9.6% +/- 6.4% (extremely high risk). Of the five risk factors analyzed, only the response to prednisolone monotherapy among extremely high-risk patients proved important.Early treatment intensification did not compensate for a truncated phase of maintenance chemotherapy in children with standard- or high-risk ALL. However, 6 months of antimetabolite treatment seemed adequate for extremely high-risk patients who were good responders to prednisolone and received intensified chemotherapy that included high-dose cytarabine early in the clinical course.
Autologous marrow transplantation for malignant lymphoma: a report of 101 cases from Seattle.
Authors: F B Petersen, F R Appelbaum, R Hill, L D Fisher, C L Bigelow, J E Sanders, K M Sullivan, W I Bensinger, R P Witherspoon, R Storb
Journal: Journal of Clinical Oncology (1990)

Between October 1979 and January 1988, 101 patients with malignant lymphoma who failed initial induction treatment or relapsed received high-dose combination chemotherapy or chemoradiotherapy followed by infusion of autologous bone marrow. Twenty-eight of the 101 patients survive, 18 of whom are disease-free for a median of 26 (range, 12 to 66) months. The 5-year actuarial probabilities of survival, event-free survival (EFS), and relapse from transplantation were 20%, 11%, and 84%, respectively. Multivariate analysis showed that the likelihood of EFS was decreased among patients transplanted with a Karnofsky score of less than 80%. Recurrent lymphoma after transplant was the most important cause of treatment failure with 36 of 62 relapses occurring within 100 days from marrow infusion. Early, but not late relapse, was more frequent in patients transplanted for advanced lymphoma, and both early and late relapses were increased among patients with impaired pretransplant clinical performance or high-grade histology of lymphoma. Ten patients who relapsed post-transplant are alive, seven in remission. Further improvement of these results will require earlier transplantation, improved preparative regimens, or early posttransplant therapy.
Decitabine (DAC) in combination with doxorubicin (DOX) and cyclophosphamide (CTX) in relapsed neuroblastoma (NBL): A Children's Oncology Group Study
Authors: R. George, J. Lahti, M. Ingle, M. Krailo, S. Blaney, P. Adamson, A. Murgo, V. Kidd, L. Diller
Journal: Journal of Clinical Oncology (2007)

9565 Background: Loss of caspase-8 expression causes resistance to apoptosis-inducing agents and potentiates metastasis in NBL. In vitro treatment of NBL cell lines with DAC results in increased caspase-8 expression and enhanced apoptosis following exposure to DOX. As a component of a pediatric phase 1 study, we evaluated low-dose DAC with DOX and CTX in a cohort of children with relapsed NBL. Promoter specific DNA methylation in peripheral blood mononuclear cells (PBMC) was studied. Methods: Patients received a 1-hour infusion of DAC, 5 mg/m 2 , daily on days 0–6, followed on day 7 by 45 mg/m 2 of DOX (with dexrazoxane) and 1 g/m 2 of CTX. All patients received G-CSF. Cycles were repeated every 28 days. Methylation-specific and quantitative PCR were used to measure promoter-specific DNA methylation in PBMC prior to and after DAC (day 7 and day 28). Results: Twelve patients with recurrent NBL (median age 9 years, 10 males) were enrolled. DAC/DOX/CTX was well tolerated with grade 4 myelosuppression being the predominant toxicity. Grade 4 neutropenia, median 11 days duration, occurred in 10 pts and grade 4 thrombocytopenia, median 10 days, in 7 patients. Eight patients had progressive disease after = 2 courses of therapy. The remaining 4 patients had stable disease with 5 to 8 courses. Methylation and subsequent demethylation (40–90% decreased methylation) of the MAGE-1 promoter was detected before and after DAC respectively, in PBMC from 6 of 9 patients analyzed to date. Re-expression of MAGE-1 mRNA was also demonstrated in post treatment samples. Caspase-8 demethylation was not detected in PBMC; nor was hypermethylation of caspase-8 detected in pre-treatment PBMC, possibly due to low tumor burden in blood. Conclusions: DAC in combination with cytotoxic chemotherapy was relatively well tolerated in heavily pre-treated children with relapsed NBL. Low-dose DAC induces demethylation and re-expression of MAGE-1 in PBMC, and may be a potential surrogate marker of demethylation within tumor cells. The use of low dose DAC in combination with other agents warrants further study in NBL. No significant financial relationships to disclose.
PDGFRα and β Play Critical Roles in Mediating Foxq1-Driven Breast Cancer Stemness and Chemoresistance
Authors: Fanyan Meng, Cecilia L. Speyer, Bin Zhang, Yongzhong Zhao, Wei Chen, David H. Gorski, Fred R. Miller, Guojun Wu
Journal: Cancer Research (2014)

Many epithelial-mesenchymal transition (EMT)-promoting transcription factors have been implicated in tumorigenesis and metastasis as well as chemoresistance of cancer. However, the underlying mechanisms mediating these processes are unclear. Here, we report that Foxq1, a forkhead box-containing transcription factor and EMT-inducing gene, promotes stemness traits and chemoresistance in mammary epithelial cells. Using an expression profiling assay, we identified Twist1, Zeb2, and PDGFRα and β as Foxq1 downstream targets. We further show that PDGFRα and β can be directly regulated by Foxq1 or indirectly regulated through the Foxq1/Twist1 axis. Knockdown of both PDGFRα and β results in more significant effects on reversing Foxq1-promoted oncogenesis in vitro and in vivo than knockdown of either PDGFRα or β alone. In addition, PDGFRβ is a more potent mediator of Foxq1-promoted stemness traits than PDGFRα. Finally, pharmacologic inhibition or gene silencing of PDGFRs sensitizes mammary epithelial cells to chemotherapeutic agents in vitro and in vivo. These findings collectively implicate PDGFRs as critical mediators of breast cancer oncogenesis and chemoresistance driven by Foxq1, with potential implications for developing novel therapeutic combinations to treat breast cancer.
Survival of infants with primitive neuroectodermal tumors or malignant ependymomas of the CNS treated with eight drugs in 1 day: a report from the Childrens Cancer Group.
Authors: J R Geyer, P M Zeltzer, J M Boyett, L B Rorke, P Stanley, A L Albright, J H Wisoff, J M Milstein, J C Allen, J L Finlay
Journal: Journal of Clinical Oncology (1994)

Very young children with CNS primitive neuroectodermal tumors (PNETs) and ependymomas have a poor prognosis and commonly have impairment of growth and cognitive abilities, in part resulting from radiotherapy. Thus, an intensive chemotherapeutic regimen was used to treat children less than 18 months of age at diagnosis.Children were treated on a Childrens Cancer Group (CCG) protocol with an eight-drug chemotherapeutic regimen (vincristine, carmustine, procarbazine, hydroxyurea, cisplatin, cytarabine, prednisone, and cyclophosphamide) following surgery and postoperative staging. Delayed or reduced-volume radiotherapy was to be administered to all patients, but, in fact, was omitted in most cases.On central review of pathology, 82 children had diagnosis concordant with study entry criteria. Of these, 46 (56%) had posterior fossa (PF) PNET, eight (10%) had pineal PNET, 11 (12%) had nonpineal supratentorial PNET, 15 (18%) had ependymoma, and two had rhabdoid tumors. Fifty percent of tumor resections were complete, as verified by postoperative computed tomographic (CT) scan, and 23% of patients had metastatic disease at the time of diagnosis. Objective tumor response was documented following two cycles of chemotherapy in 28% of assessable patients. Toxicity of chemotherapy was primarily hematopoietic. Five children died of chemotherapy-related complications. Radiotherapy was administered to only nine patients before tumor progression. The 3-year progression-free survival (PFS) rates for PF PNET, pineal PNET, supratentorial nonpineal PNET, and ependymoma are 22% (SE = 6%), 0%, 55% (16%), and 26% (11%), respectively. The 3-year PFS rate for those children without metastatic disease was 29% (6%), as compared with 11% (6%) for those with metastatic disease. The only independent predictors of PFS were metastasis stage and location of the tumor within the pineal region. The median time to progression was 6 months. Twenty-four children completed the chemotherapeutic regimen without tumor progression; 19 are event-free survivors more than 2 years from diagnosis, only three of whom received radiation therapy.While overall survival in this group of very young patients is poor, a subset of children who have received only chemotherapy as adjuvant treatment remain free from tumor recurrence.
Adipocyte iron regulates leptin and food intake
Authors: Yan Gao, Zhonggang Li, J. Scott Gabrielsen, Judith A. Simcox, Soh-hyun Lee, Deborah Jones, Bob Cooksey, Gregory Stoddard, William T. Cefalu, Donald A. McClain
Journal: Journal of Clinical Investigation (2015)

Dietary iron supplementation is associated with increased appetite. Here, we investigated the effect of iron on the hormone leptin, which regulates food intake and energy homeostasis. Serum ferritin was negatively associated with serum leptin in a cohort of patients with metabolic syndrome. Moreover, the same inverse correlation was observed in mice fed a high-iron diet. Adipocyte-specific loss of the iron exporter ferroportin resulted in iron loading and decreased leptin, while decreased levels of hepcidin in a murine hereditary hemochromatosis (HH) model increased adipocyte ferroportin expression, decreased adipocyte iron, and increased leptin. Treatment of 3T3-L1 adipocytes with iron decreased leptin mRNA in a dose-dependent manner. We found that iron negatively regulates leptin transcription via cAMP-responsive element binding protein activation (CREB activation) and identified 2 potential CREB-binding sites in the mouse leptin promoter region. Mutation of both sites completely blocked the effect of iron on promoter activity. ChIP analysis revealed that binding of phosphorylated CREB is enriched at these two sites in iron-treated 3T3-L1 adipocytes compared with untreated cells. Consistent with the changes in leptin, dietary iron content was also directly related to food intake, independently of weight. These findings indicate that levels of dietary iron play an important role in regulation of appetite and metabolism through CREB-dependent modulation of leptin expression.
Improved survival in patients with poor-prognosis malignant melanoma treated with adjuvant levamisole: a phase III study by the National Cancer Institute of Canada Clinical Trials Group.
Authors: I C Quirt, W E Shelley, J L Pater, A J Bodurtha, P B McCulloch, T A McPherson, A H Paterson, R Prentice, H K Silver, A R Willan
Journal: Journal of Clinical Oncology (1991)

Five hundred forty-three patients with completely resected malignant melanoma who were considered to have a significant risk of developing recurrent disease were randomized to one of four study groups. One group received levamisole 2.5 mg/kg on 2 consecutive days weekly for 3 years, a second group received bacillus Calmette-Guérin (BCG) for 3 years. A third group alternated 8-week courses of BCG and levamisole for 3 years and a fourth group underwent clinical assessment at the same frequency as the three treatment groups. The median duration of follow-up is 8.5 years. The percentage of reduction in the death rate and the recurrence rate in the treatment groups compared with the control group was calculated using the Cox proportional hazards model and adjusted for age, sex, and stage as covariants. The patients treated with levamisole were estimated to have a 29% reduction in both the death rate (P = .08) and the recurrence rate (P = .09) compared with patients receiving no further treatment. Fifty-five patients discontinued levamisole early because of gastrointestinal intolerance or arthralgia, myalgia, fever, and immune leukopenia. The patients treated with BCG alternating with levamisole experienced a 10% reduction in the death rate and a 6% reduction in the recurrence rate, and the patients treated with BCG alone experienced a 4% reduction in the death rate and a 3% increase in the recurrence rate compared with the control group. The degree of improvement experienced by the patients that were treated by levamisole is of sufficient magnitude to warrant further investigation of this dose of levamisole as adjuvant treatment in patients with melanoma.
CoMEt: a statistical approach to identify combinations of mutually exclusive alterations in cancer
Authors: Mark DM Leiserson, Hsin-Ta Wu, Fabio Vandin, Benjamin J. Raphael
Journal: Genome biology (2015)

Cancer is a heterogeneous disease with different combinations of genetic alterations driving its development in different individuals. We introduce CoMEt, an algorithm to identify combinations of alterations that exhibit a pattern of mutual exclusivity across individuals, often observed for alterations in the same pathway. CoMEt includes an exact statistical test for mutual exclusivity and techniques to perform simultaneous analysis of multiple sets of mutually exclusive and subtype-specific alterations. We demonstrate that CoMEt outperforms existing approaches on simulated and real data. We apply CoMEt to five different cancer types, identifying both known cancer genes and pathways, and novel putative cancer genes.
No evidence of Legionella infection in general practice patients presenting with acute respiratory infections in The Netherlands
Authors: B.M.W. Diederen, C.M.A. de Jong, I. Aarts, M.F. Peeters, A.B. van Gageldonk-Lafeber, B. Wilbrink, A. van der Zee
Journal: Clinical Microbiology and Infection (2005)
Coronary Computed Tomography Angiography Versus Radionuclide Myocardial Perfusion Imaging in Patients With Chest Pain Admitted to Telemetry
Authors: Jeffrey M. Levsky, Daniel M. Spevack, Mark I. Travin, Mark A. Menegus, Paul W. Huang, Elana T. Clark, Choo-won Kim, Esther Hirschhorn, Katherine D. Freeman, Jonathan N. Tobin, Linda B. Haramati
Journal: Annals of Internal Medicine (2015)

The role of coronary computed tomography angiography (CCTA) in the management of symptomatic patients suspected of having coronary artery disease is expanding. However, prospective intermediate-term outcomes are lacking.To compare CCTA with conventional noninvasive testing.Randomized, controlled comparative effectiveness trial. (ClinicalTrials.gov: NCT00705458).Telemetry-monitored wards of an inner-city medical center.400 patients with acute chest pain (mean age, 57 years); 63% women; 54% Hispanic and 37% African-American; and low socioeconomic status.CCTA or radionuclide stress myocardial perfusion imaging (MPI).The primary outcome was cardiac catheterization not leading to revascularization within 1 year. Secondary outcomes included length of stay, resource utilization, and patient experience. Safety outcomes included death, major cardiovascular events, and radiation exposure.Thirty (15%) patients who had CCTA and 32 (16%) who had MPI underwent cardiac catheterization within 1 year. Fifteen (7.5%) and 20 (10%) of these patients, respectively, did not undergo revascularization (difference, -2.5 percentage points [95% CI, -8.6 to 3.5 percentage points]; hazard ratio, 0.77 [CI, 0.40 to 1.49]; P = 0.44). Median length of stay was 28.9 hours for the CCTA group and 30.4 hours for the MPI group (P = 0.057). Median follow-up was 40.4 months. For the CCTA and MPI groups, the incidence of death (0.5% versus 3%; P = 0.12), nonfatal cardiovascular events (4.5% versus 4.5%), rehospitalization (43% versus 49%), emergency department visit (63% versus 58%), and outpatient cardiology visit (23% versus 21%) did not differ. Long-term, all-cause radiation exposure was lower for the CCTA group (24 versus 29 mSv; P < 0.001). More patients in the CCTA group graded their experience favorably (P = 0.001) and would undergo the examination again (P = 0.003).This was a single-site study, and the primary outcome depended on clinical management decisions.The CCTA and MPI groups did not significantly differ in outcomes or resource utilization over 40 months. Compared with MPI, CCTA was associated with less radiation exposure and with a more positive patient experience.American Heart Association.
Consensus recommendations for a standardized Brain Tumor Imaging Protocol in clinical trials
Authors: Benjamin M Ellingson, Martin Bendszus, Jerrold Boxerman, Daniel Barboriak, Bradley J Erickson, Marion Smits, Sarah J Nelson, Elizabeth Gerstner, Brian Alexander, Gregory Goldmacher, Wolfgang Wick, Michael Vogelbaum, Michael Weller, Evanthia Galanis, Jayashree Kalpathy-Cramer, Lalitha Shankar, Paula Jacobs, Whitney B Pope, Dewen Yang, Caroline Chung, Michael V Knopp, Soonme Cha, Martin J van den Bent, Susan Chang, W K Al Yung, Timothy F Cloughesy, Patrick Y Wen, Mark R Gilbert
Journal: Neuro-Oncology (2015)

A recent joint meeting was held on January 30, 2014, with the US Food and Drug Administration (FDA), National Cancer Institute (NCI), clinical scientists, imaging experts, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocate groups to discuss imaging endpoints for clinical trials in glioblastoma. This workshop developed a set of priorities and action items including the creation of a standardized MRI protocol for multicenter studies. The current document outlines consensus recommendations for a standardized Brain Tumor Imaging Protocol (BTIP), along with the scientific and practical justifications for these recommendations, resulting from a series of discussions between various experts involved in aspects of neuro-oncology neuroimaging for clinical trials. The minimum recommended sequences include: (i) parameter-matched precontrast and postcontrast inversion recovery-prepared, isotropic 3D T1-weighted gradient-recalled echo; (ii) axial 2D T2-weighted turbo spin-echo acquired after contrast injection and before postcontrast 3D T1-weighted images to control timing of images after contrast administration; (iii) precontrast, axial 2D T2-weighted fluid-attenuated inversion recovery; and (iv) precontrast, axial 2D, 3-directional diffusion-weighted images. Recommended ranges of sequence parameters are provided for both 1.5 T and 3 T MR systems.
How to read a receiver operating characteristic curve
Authors: P. Sedgwick
Journal: BMJ (2015)

Researchers investigated the use of vital signs as a screening test to identify brain lesions in patients with impaired consciousness. The setting was an emergency department in Japan. In total, 529 consecutive patients presenting with impaired consciousness, as assessed by a score of less than 15 on the Glasgow coma scale, were studied. Patients were followed until discharge. The vital signs of systolic and diastolic blood pressure plus pulse rate were recorded on arrival. The diagnosis of a brain lesion was determined on the basis of brain imaging and neurological examination. In total, 312 patients (59%) were diagnosed with a brain lesion.1 The performance of each vital sign as a screening test for diagnosed brain lesions was evaluated separately. The measurement scale for each vital sign was categorised using equal sized strata. Each stratum for a vital sign was taken successively as the threshold between a "negative" and "positive" screening test result; all measurements with values greater than the categorised strata were considered a "positive" result and all others were considered "negative." If the result was positive, the patient was deemed at "high risk" of a brain lesion; otherwise the patient was deemed at "low risk" of a brain lesion. For each stratum of a vital sign the sensitivity and specificity were derived and used to plot a receiver operating characteristic curve for the vital sign (figure⇓). The area beneath the curve was 0.90 for systolic blood pressure, 0.82 for diastolic pressure, and 0.63 for pulse rate. Receiver operating characteristic curves for each of the three vital signs as screening tests for diagnosed brain lesions. For each vital sign, selected cut-off points between a positive and negative screening test result are shown Which of the following statements, if any, are true?
Phase Ib Study of Plx3397, a Csf1R Inhibitor, and Paclitaxel in Patients with Advanced Solid Tumors
Authors: H.S. Rugo, N. Sharma, L. Reebel, M.B. Rodal, A. Peck, B.L. West, A. Marimuthu, D.A. Karlin, A. Dowlati, M.H. Le, L.M. Coussens, R. Wesolowski
Journal: Annals of Oncology (2014)
Cell Proliferation and Atrophic Gastritis in Explanted Canine Gastric Mucosa2
Authors: Pierre-Paul Casteleyn, Gérard Willems
Journal: JNCI Journal of the National Cancer Institute (1975)

We produced experimental atrophic gastritis in 7 mongrel dogs by explanting a full-thickness wedge of vascularized mucosa from the gastric greater curvature onto the abdominal wall. Autoradiography of mucosal specimens was done after the iv injection of triated thymidine. The labeling index, S-phase duration, and cell cycle time were measured in normal and explanted fundic mucosa. The spatial distribution histograms of the labeled cells showed an enlarged are of proliferation. As in human atrophic gastritis, proliferation was shifted toward the mucosal surface. Significantly higher labeling indices were observed in the atrophic mucosa. Shortening of the S-phase duration and the cell cycle time was indicated by the curves of the labeled mitoses. Proliferative activity was significantly accelerated in this experimental model of atrophic gastritis.