tbuckley/cabot-search huggingface dataset:
Lexatumumab: Results of a phase I trial in pediatric patients with advanced solid tumors.
Authors: M. S. Merchant, A. J. Chou, A. Price, J. I. Geller, M. Tsokos, C. Graham, A. Charles, P. A. Meyers, C. Mackall
Journal: Journal of Clinical Oncology (2010)

9500 Background: Lexatumumab is an agonist, fully-human monoclonal antibody against TNF-Related Apoptosis Inducing Ligand Receptor 2 (TRAIL-R2) with preclinical evidence of activity in several pediatric solids tumors. A phase I trial in adult patients with solid tumors revealed a maximum tolerated dose of 10mg/kg IV every 14 days. Methods: This pediatric phase I, dose escalation study examined the safety, tolerability, pharmacokinetics, and immunogenicity of lexatumumab administered every 2 weeks to patients 21 years old and younger with recurrent or progressive solid tumors. Patient received increasing doses of lexatumumab (3, 5, 8, 10mg/m2) in a 3 + 3 design. Tumors were measured after 4 weeks, then every 2 months. Treatment was continued until disease progression or unacceptable toxicity. The expanded cohort at the maximum tolerated dose included 6 children (2-12yo) and 6 adolescents (13-21yo). Results: Twenty four patients received a total of 57 cycles of lexatumumab to date over 4 dose levels (3, 5, 8, and 10mg/kg q14days; 1 cycle = 28days). Stable disease occurred in 5 patients for 3 to 17 cycles. One patient had grade 2 pericarditis consistent with radiation recall, and one patient developed a grade 3 pneumonia with hypoxia during the second cycle of study drug. One patient with unresectable osteosarcoma pulmonary metastases continues on Lexatumumab 10mg/kg at 35+ doses (17+ cycles) with stable disease and marked clinical improvement. Transient clinical activity was observed in a patient with hepatoblastoma and Ewing sarcoma. Conclusions: Lexatumumab is well tolerated and can be safely administered every 14 days in pediatric patients. Pediatric patients tolerate 10 mg/kg, the maximum tolerated dose identified in adults. No significant financial relationships to disclose.
Endogenous particles in exhaled air – Variability of particle number in healthy individuals
Authors: Ann-Charlotte Almstrand, Per Larsson, Anna Bredberg, Ekaterina Mirgorodskaya, Anna-Carin Olin
Journal: European Respiratory Journal (2012)

Endogenous particles in exhaled air (PEx) are formed during airway reopening following airway closure. Analysis of PEx may be used for monitoring biochemical alterations in respiratory tract lining fluid in the small airways. The number of exhaled particles is strongly dependent on breathing pattern but there is also a substantial difference between individuals.  The aim of the study was to assess intra-individual variability of PEx number using a standardized breathing maneuver involving airway closure.  10 healthy subjects participated in the study. They were instructed to exhale slowly and completely, inhale to total lung capacity and exhale at 500 ml/s until functional residual capacity. Particles were counted in the final exhalation of the maneuver using an in-house developed instrument. The maneuver was repeated until 80 liters of exhaled air had been sampled. Sampling was performed 3 times (two mornings and one afternoon) for each subject.  The average total number of PEx varied from 9700 to 93 000 particles/exhalation among individuals. The coefficient of variation of total PEx number/exhalation within individuals was 3.9-36%, median 21%. The coefficient of variation between individuals was 65%. There was no intra-individual difference in particle numbers between morning and afternoon samplings.  The variability of PEx number was substantially higher between individuals than within individuals. The high variability between individuals may be due to differences in lung architecture and possibly to differences in the chemical composition of airway lining fluid. Our results support the fact that it is important to control for mass of PEx for any given concentration of non-volatile analyte.
Residual disease detection using fluorescent polymerase chain reaction at 20 weeks of therapy predicts clinical outcome in childhood acute lymphoblastic leukemia.
Authors: P A Evans, M A Short, R G Owen, A S Jack, P D Forsyth, C R Shiach, S Kinsey, G J Morgan
Journal: Journal of Clinical Oncology (1998)

PURPOSE Ninety-five percent of children with acute lymphoblastic leukemia (ALL) will achieve a remission, but approximately 25% will relapse. Identifying these patients is difficult, as patients with adverse prognostic features at presentation are rare and the majority are standard risk. Analysis of minimal residual disease (MRD) may be able to determine those at risk of relapse, but the best method by which this can be accomplished has yet to be defined. The object of this study was to determine the predictive value of residual disease detection in a group of standard-risk patients with precursor-B ALL at a fixed point in therapy (week 20) using a simple fluorescent consensus immunoglobulin H (IgH) heavy chain polymerase chain reaction (PCR). PATIENTS AND METHODS Forty-two patients who presented with precursor-B ALL with standard-risk clinical features and treated according to either the Medical Research Council (MRC) UKALL X or XI protocols were assessed using a combination of both fluorescent consensus framework I and framework III Ig heavy-chain PCR. The results of the PCR were analyzed on an ABI 373 gene sequencer with genescan software (Applied Biosystems, Foster City, CA). Clonal rearrangements detected at presentation were looked for at week 20. RESULTS Of 42 patients, 35 had a clonal population detectable at presentation; of these, seven had more than two clonal rearrangements; this latter group showed a similar disease-free survival (DFS) to the group as a whole. Thirty of 35 patients were analyzed before their second course of intensification therapy at week 20. At this point, nine of 30 had a detectable clonal rearrangement, eight (89%) of whom have since relapsed with a median DFS of 27.5 months. Of the rest of the group (n=21), in whom no clonal rearrangement was detectable, only six (21%) have relapsed. CONCLUSION Fluorescent IgH PCR at week 20 provides a sensitive and specific means to predict ultimate relapse (57% and 89%, respectively) and is a simple yet promising technique for the identification of patients at risk of poor outcome.
Intraoperative, adjuvant treatment of gastric cancer with the trifunctional antibody catumaxomab compared to surgery alone: A phase II study
Authors: C. M. Krueger, B. A. Berdov, L. A. Roman, A. V. Luft, P. Lampe, H. Lindhofer, K. Bartelheim, A. Klein, M. M. Heiss
Journal: Journal of Clinical Oncology (2008)

15529 Background: Gastric cancer patients (pts) have a high risk of peritoneal recurrence due to disseminated tumor cells after surgery. The trifunctional antibody catumaxomab (anti-EpCAM × anti-CD3) administered locally into the peritoneal cavity aims at residual tumor cells while activating a complex anti-tumor immune reaction. Methods: A total of 55 gastric cancer pts (T2b/T3/T4, N±, M0) were randomized during surgical D2 procedure to surgery alone or catumaxomab administered as one intraoperative intraperitoneal (ip) and 4 postoperative ip infusions with ascending doses on day 7, 10, 13 and 16. Primary objectives were safety, tolerability and feasibility. Results: All 55 pts (27 surgery alone, 28 catumaxomab) were included in the safety analysis. The target antigen EpCAM was confirmed in 100 % of pts. 78 % (22/28) of the patients treated with catumaxomab received all 5 infusions. 40 % of the treatment-emergent adverse events (TEAEs) occurred directly after the intraoperative administration. TEAEs (CTC-grade ≥3) occurred in 22 patients (control arm: 10 patients). The most frequently TEAEs in the catumaxomab group were anemia, pyrexia, SIRS and abdominal pain. All related serious TEAEs resolved until end of treatment except for nephropathy (one patient), which resolved with minor sequelae. No trend of an accumulation of severe adverse reactions or complications (e.g. wound healing) occurred compared to the surgery only group. Conclusions: Adjuvant treatment of ip administration of catumaxomab is safe and well-tolerable in pts after curative resection, the safety results reflecting catumaxomab´s mode of action (cytokine release related symptoms). This offers a new chance to avoid intraabdominal tumor recurrence. First clinically relevant efficacy data will be obtained after the 1- and 2-year follow-up period. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Fresenius Biotech GmbH Fresenius Biotech GmbH Fresenius Biotech GmbH Fresenius Biotech GmbH
Biology of Hepatocellular Neoplasia In the Mouse. III. Electron Microscopy of Safrole-Induced Hepatocellular Adenomas and Hepatocellular Carcinomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: Michael M. Lipsky, David E. Hinton, James E. Klaunig, Benjamin F. Trump
 7
Journal: JNCI Journal of the National Cancer Institute (1981)

A systematic, ultrastructural analysis was performed on safrole-induced hepatocellular adenomas and hepatocellular carcinoma(s) (HPC) in BALB/c mice. Adenomas were heterogeneous in cell composition containing dark-staining basophilic cells, pale-staining acidophilic cells, clear cells, and lipid-laden cells. Darkly staining cells resembled fetal hepatocytes. They had large nuclei with irregular borders and limited diversity of organelles. Rough endoplasmic reticulum was prominent and seen as parallel cisternae in single or double tracts often in association with mitochondria. Pale-staining cells contained abundant smooth endoplasmic reticulum. Other organelles were often displaced to the perinuclear or peripheral region of the cell. The clear cells resembled dark-staining or pale-staining cells but also contained large areas of glycogen deposition. Lipid-laden cells contained numerous, multisized lipid droplets in the cytoplasm. HPC contained cell types similar to those of the adenoma. In addition, they contained many anaplastic cells. These resembled hepatocytes but contained several other alterations. The most striking was an apparent increase in the number of altered mitochondria. The cytoplasm was often filled with enlarged mitochondria with dense or pale matrices. The cristae were few and had altered configurations. Also, an apparent increase was seen in the number of microbodies. These were often clustered in one region of the cytoplasm. An increase in microbodies was also noted in other cell types of hepatocellular carcinomas. The results of this study demonstrated similarities in the cell types of the adenomas and HPC. This study also demonstrated differences, with the anaplastic cell being common only to the carcinoma. Due to the similarity of cell types, the adenoma should be considered a possible site of HPC developmen
Current Approaches in Familial Colorectal Cancer: A Clinical Perspective
Authors: Patrick M. Lynch
Journal: Journal of the National Comprehensive Cancer Network (2006)

Individuals with a family history of colorectal cancer or colorectal adenomas have an increased risk for colorectal cancer. When no hereditary syndrome is evident, screening is based on empiric risk estimates. The risk is greatest for individuals with specific inherited cancer-predisposing disorders. When conditions such as familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer are diagnosed, specific neoplasm risk estimates can usually be performed based on advances in molecular genetics. These estimates lead to more straightforward and cost-effective approaches to surveillance and management. The National Comprehensive Cancer Center Network (NCCN) and other groups have provided detailed guidelines for evaluating patients based on recognition of clinical syndrome characteristics, followed by appropriate genetic counseling, genetic testing, and optimal surveillance. The NCCN guidelines are used as a frame of reference for this discussion of selected recent advances in human cancer genetics as they apply to clinical practice.
Abstract 12404: Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation and Normal Renal Function over Time: Insights From the ARISTOTLE Trial
Authors: Ziad Hijazi, Stefan H. H Hohnloser, Ulrika Andersson, John H Alexander, Christopher B Granger, Michael Hanna, Matyas Keltai, Alexander Parkhomenko, Jose L Lopez-Sendon, Renato D Lopes, Agneta Siegbahn, Lars Wallentin
Journal: Circulation (2015)

Introduction: It has been recently observed that one oral factor-Xa inhibitor (at the dose studied) might be associated with decreased efficacy in patients with atrial fibrillation (AF) and normal renal function. In the ARISTOTLE trial, apixaban compared to warfarin reduced stroke, mortality, and major bleeding irrespective of renal function at baseline. Our aim was to evaluate the efficacy and safety of apixaban vs. warfarin in patients with normal renal function over time. Methods: In ARISTOTLE, 16,971 patients had serial creatinine measurements available after randomization. There were a total of 397 stroke or systemic embolic events, 286 ischemic or unspecified strokes, and 712 major bleed events during median follow-up of 1.8 years. Normal renal function was predefined as an estimated glomerular filtration rate (eGFR) &gt;80 mL/min. The relations between renal function, treatment, and outcomes were investigated by using Cox regression with renal function as a continuous time dependent covariate, fitted using restricted splines. Hazard ratios with 95% confidence intervals (CI) were analyzed based on continuous eGFR level during follow-up using both the Cockcroft-Gault and CKD-EPI equations. Results: The relative risk of stroke or systemic embolism was consistently lower in participants randomized to apixaban compared with warfarin. The patterns were similar for the ischemic or unspecified stroke outcome as well as for major bleeding (Table). Conclusions: Apixaban, relative to warfarin, demonstrated preserved efficacy and safety in AF patients with normal renal function over time.
Osteoclast-Derived Zinc Finger (OCZF) Protein With POZ Domain, a Possible Transcriptional Repressor, Is Involved in Osteoclastogenesis
Authors: Akiko Kukita, Toshio Kukita, Mamoru Ouchida, Hidefumi Maeda, Hitomi Yatsuki, Osamu Kohashi
Journal: Blood (1999)
Pharmacoeconomic study in head and neck cancer patients: Impact of prospective DPD deficiency screening with 5-fluorouracil (5-FU) dose tailoring on toxicities-related costs
Authors: C. Mercier, C. Brunet, C. Yang, C. Dupuis, D. Bagarry-Liegey, S. Duflo, A. Giovanni, M. Zanaret, B. Lacarelle, F. Duffaud, J. Ciccolini
Journal: Journal of Clinical Oncology (2009)

6515 Background: Dihydropyrimidine dehydrogenase (DPD) plays a pivotal role in the detoxification of 5-FU. We studied the impact of screening DPD impairment in head and neck cancer (HNC) patients, both on reduction of drug-related toxicities and as a pharmacoeconomic endpoint. Methods: A total of 148 consecutive patients with HNC treated with 5-FU+platinum were monitored. Seventy-four patients (Arm A - before 2006) were treated with standard dosage, whereas 74 other patients (Arm B - after 2006) had their DPD status phenotypically evaluated prior to receiving 5-FU, with subsequent dose reduction if DPD deficiency were suspected. Severe toxicities and response were compared. Additionally, direct and indirect costs required to manage the treatment-related toxicities and to establish DPD status were calculated. Results: Sepsis was observed in 16.2% of patients treated with standard dosage. In Arm B, DPD deficiency was suspected in 35% of the patients and 5-FU dosage was subsequently reduced. Consequently, only 1.8% of them experienced sepsis. Of note, response rates were comparable between Arm A and B (62 vs 61%, p&gt;0.05), thus demonstrating that 5-FU dose tailoring did not negatively impact on treatment efficacy, while reducing the occurrence of severe toxicities. Managing toxicities required an average 23-days of extra-hospitalization (4–96 days), including an average 1.6-day stay in ICU. No patients from Arm B had to stay in ICU. Drugs required for managing toxicities cost an average of $339 per patient (Arm A) and was reduced down to $38 per patient (Arm B). Similarly, mean extra-hospitalization cost was $5,940/patient in Arm A and $245/patient in Arm B. Testing DPD cost $49/patient in Arm B. Conclusions: Developing an adaptative dosing strategy based upon DPD status evaluation led to a dramatic reduction of the incidence of 5-FU-related severe toxicities, while maintaining optimal efficacy. Subsequently, extra-cost (medication + hospitalization costs) required to manage the toxicities fell down from $6,279 to $294/patient. Overall, this study advocates that systematic screening for DPD deficiency could be cost-efficient in the setting of 5-FU-based chemotherapies, with a reduction of 95% of the extra-costs. No significant financial relationships to disclose.
Chemotherapy dose delivery in elderly patients with lung and colon cancer; a single institution study
Authors: A. Bhargava, N. Seetharamu, S. Shrestha, B. Mehrotra
Journal: Journal of Clinical Oncology (2004)

8261 Background: Chemotherapy dose delivery in the elderly is a challenge. Often, elderly patients undergo surgery but not all receive adjuvant or palliative chemotherapy despite proven benefit of these regimens to improve survival. The purpose of our study was to analyze the practice patterns of chemotherapy dose ordering and delivery in patients with ages 70 years and above who were diagnosed with lung or colorectal cancer (CRC) at our institution. Methods: A retrospective review of chemotherapy charts was performed for patients identified over the age of 70 years with a diagnosis of CRC and lung cancer at our institution from 1998–2002. The Institutional Review Board approved the study. We studied the chemotherapy regimens, dose modifications and concurrent use of radiation therapy in lung cancer and CRC. Frequency of growth factor support utilization was identified. Results: 36 patients were identified who received chemotherapy (n=21 lung ca; n=15 CRC). Median age of all patients was 75 yrs (range 70–85 years); M: F 6:15 (lung ca), 7:8 (CRC). Performance status of all pts. 0–2 (ECOG). Stage distribution: lung ca (IIIA n=5; IIIB n=9, IV n=5, small cell lung ca n=2). CRC (high risk II n=8, III n=5, IV n=2). 12 of 21 pts.treated for lung ca received concurrent chemotherapy and radiation therapy. All 12 patients received standard regimens but only 3/12 (25%) received standard doses of carboplatin and paclitaxel. 4/12 (33%) were treated with a single drug, carboplatin or paclitaxel with radiation. 8/14 (57%) pts completed 5 weeks or more of planned radiation treatment. Analysis of CRC pts: 7/15(46 %) received a standard regimen (5FU/ Leucovorin). Doses were initially reduced by 10% in all. 2 pts required further dose reductions of 5-FU and Leucovorin secondary to diarrhea. 11/36 (30%) pts required G-CSF supplementation. 23/36 pts. (64%) required erythropoietin support. Conclusions: Elderly patients require significant dose reductions and modifications to tolerate chemotherapy +/- XRT safely and are frequently unable to complete proposed treatments. The impact of established treatment regimens on survival in elderly patients needs to be further investigated No significant financial relationships to disclose.
The garden in our gut
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

This agar dish has been created by allowing tiny amounts of the bacteria Citrobacter (turquoise), Escherichia coli (purple), and multidrug resistant Klebsiella (dark blue) to grow overnight, replicating what happens naturally in the gut, where the “good” bacteria keep the more harmful “bad” ones under control.

The bottom disc contains co-amoxiclav, …
Efficacy and Safety of Maintenance Bevacizumab (Bev) with or Without Capecitabine (Cap) After Initial First-Line Bev Plus Docetaxel (Doc) for Her2-Negative Metastatic Breast Cancer (Mbc): Imelda Randomised Phase III Trial
Authors: J. Gligorov, D. Doval, J. Bines, Z. Jiang, E. Alba, P. Cortes, S. Srock, S. de Ducla, U. Freudensprung, G. Mustacchi
Journal: Annals of Oncology (2014)
Quality of life in stage II breast cancer: an instrument for clinical trials.
Authors: M N Levine, G H Guyatt, M Gent, S De Pauw, M D Goodyear, W M Hryniuk, A Arnold, B Findlay, J R Skillings, V H Bramwell
Journal: Journal of Clinical Oncology (1988)

A questionnaire has been developed for use as an outcome measure in clinical trials of adjuvant chemotherapy in women with stage II breast cancer. The selection of items for this Breast Cancer Chemotherapy Questionnaire (BCQ) was based on the problems and experiences felt to be most important by women undergoing adjuvant chemotherapy. The BCQ consists of 30 questions that focus on loss of attractiveness, fatigue, physical symptoms, inconvenience, emotional distress, and feelings of hope and support from others. The BCQ, other instruments that evaluate quality-of-life (Spitzer, Karnofsky, and Rand), and patient and physician global assessments were administered serially to 418 patients taking part in a randomized trial comparing a 12-week regimen and a 36-week regimen of adjuvant chemotherapy. The validity of the BCQ is supported by its correlation with the Rand Emotional (r = .58), Rand Physical (r = .60), and Spitzer (r = .62) questionnaires. The BCQ correlated more strongly with global ratings of both physical and emotional function by the patients and their physicians than the other instruments. A comparison of the quality-of-life outcomes of patients in the two treatment groups in the period beyond 3 months after initiation of treatment, when one group had completed the treatment course and the other was still on treatment, revealed that the BCQ and Karnofsky were the only instruments able to demonstrate differences between the groups (P less than .0001). Hence, the BCQ is a valid and responsive method of assessing treatment-related morbidity in patients receiving adjuvant chemotherapy for stage II breast cancer.
The Smad5 Gene Is Involved in the Intracellular Signaling Pathways That Mediate the Inhibitory Effects of Transforming Growth Factor-β on Human Hematopoiesis
Authors: Edward Bruno, Stephen K. Horrigan, David Van Den Berg, Elen Rozler, Priscilla R. Fitting, Steven T. Moss, Carol Westbrook, Ronald Hoffman
Journal: Blood (1998)