tbuckley/cabot-search huggingface dataset:
FcαRI (CD89) as a Novel Trigger Molecule for Bispecific Antibody Therapy
Authors: Thomas Valerius, Bernhard Stockmeyer, Annemiek B. van Spriel, Robert F. Graziano, Ingrid E. van den Herik-Oudijk, Roland Repp, Yashwant M. Deo, John Lund, Joachim R. Kalden, Martin Gramatzki, Jan G.J. van de Winkel
Journal: Blood (1997)

Abstract Promising results from clinical trials with unconjugated antibodies stimulated renewed interest in immune effector mechanisms of monoclonal antibodies (MoAbs). We investigated the potential of IgA as antibody isotype for cell- or complement-mediated tumor cell lysis and assessed the potential of its myeloid Fc receptor, FcαRI (CD89), as trigger molecule for bispecific antibody (BsAb)-mediated immunotherapy. Comparing hapten-directed antibodies of human IgA2 with IgG1 or IgG3 isotypes, we found all three to mediate effective killing of sensitized tumor target cells in whole blood assays. Analysis of effector mechanisms showed IgG-mediated lysis to be predominantly complement-dependent, whereas IgA-dependent killing was primarily effector cell-mediated. A comparison of effector cell populations in antibody-dependent cell-mediated cytotoxicity (ADCC) showed neutrophils to be most important for IgA-dependent tumor cell killing, involving FcαRI as shown with Fc receptor blocking antibodies. Reverse ADCC experiments against target cells sensitized with Fc receptor antibodies, or assays with FcαRI-directed bispecific antibodies confirmed FcαRI as effective trigger molecule in polymorphonuclear neutrophil (PMN)-mediated lysis. During granulocyte colony-stimulating factor (G-CSF ) therapy, (FcαRI × HER-2/neu) bispecific antibodies induced enhanced killing of HER-2/neu positive SK-BR–3 breast cancer cells in whole blood assays. This enhanced cytotoxicity was paralleled by increased PMN counts, which lead to higher effector to target cell ratios in G-CSF–primed blood. Furthermore, bispecific antibodies, directed to FcαRI and Candida albicans, enhanced neutrophils' phagocytosis of fungi. In summary, these results identify IgA as an effective antibody isotype for immunotherapy, working primarily via FcαRI on neutrophils. They suggest FcαRI-directed bispecific antibodies and G-CSF to be an attractive combination for malignant or infectious diseases.
Monitoring chromogranine A (CgA) serum levels during chemotherapy for hormone refractory prostate cancer (HRPC): Which impact in daily practice?
Authors: M. Timar-David, D. Pouessel, H. Huguet, P. Lamy, S. Culine
Journal: Journal of Clinical Oncology (2008)

16107 Background: Studies published in the literature on CgA serum levels suggest a possible role in the management of patients with HRPC. Methods: Data from 100 patients treated for HRPC with chemotherapy in our institution from 2002 to 2007 were retrospectively analysed. CgA serum level, clinical and biological parameters [Gleason score, performance status (PS), neuron specific enolase (NSE), prostate-specific antigen (PSA), lactate dehydrogenase (LDH), alkaline phosphatase (PAL), albumin (ALB) and hemoglobin (Hb) serum levels,] and clinical outcomes were collected. Baseline parameters (CgA and others) and their variations during chemotherapy were studied. Cox proportional hazards regression models were used for univariate and multivariate analyses. Results: Median age was 69 at time of chemotherapy. Median follow-up was 13.9 months [range, 1.7 to 53.9]. Gleason score was ≥ 7 in 86% of patients, and 47% of patients had metastases at diagnosis. The median baseline serum levels of CgA, PSA and NSE were respectively 91 ng/ml [normal (N) < 70 ng/ml], 71.5 ng/ml [N<4 ng/ml] and 8 ng/ml [N< 15 ng/ml]. A median of 6 cycles of chemotherapy per patient was delivered. The objective, PSA and neuroendocrine response rates were respectively 41%, 36% and 12%. Median overall survival (OS) was 17 months (95%CI: 13.8–19.7). In univariate analysis, PSA, ALB, CgA and Hb serum levels predicted for overall survival. In multivariate analysis, PSA and ALB confirmed their prognostic role: patients with elevated PSA but a normal ALB level had an OS of 18 months, higher than other patients (10 months). NSE serum level, Gleason score and other parameters had no impact on response or survival. There was no correlation between neuroendocrine, objective or PSA responses. Conclusions: The CgA serum level monitoring during chemotherapy has no interest in routine clinical practice. No significant financial relationships to disclose.
HLA-A, -B, -C and –DRB1 High Resolution Matching Can Improve Patient' Outcome After Double Umbilical Allogeneic Stem Cell Transplantation (allo-SCT)
Authors: Florent Malard, Katia Gagne, Patrice Chevallier, Anne Devys, Thierry Guillaume, Patricia Herry, Jacques Delaunay, Philippe Moreau, Mohamad Mohty, Anne Cesbron
Journal: Blood (2013)
A phase II study evaluating oral triamcinolone in patients with androgen independent prostate cancer
Authors: D. Feldman, S. Srinivas
Journal: Journal of Clinical Oncology (2005)

4692 Background: As patients evolve from androgen-dependent to androgen independent prostate cancer (AIPC) some develop mutations in the androgen receptor (AR) allowing the cancer to grow in the absence of androgens. A double mutation in the ligand binding domain of the AR has been described in some patients with AIPC that renders the cancer responsive to corticosteroids including cortisol and cortisone. Preclinical studies demonstrated that, as opposed to cortisol, triamcinolone did not bind or activate the mutated AR. We therefore conducted a prospective trial for patients with AIPC with oral triamcinolone to suppress endogenous cortisol and evaluate response. Objective: To assess the serum prostate specific antigen (PSA) response and the time to progression in patients with AIPC treated with triamcinolone. Methods: Patients with AIPC and rising PSA who failed other therapies and were on androgen depletion therapy with castrate levels of testosterone were prospectively treated with oral triamcinolone acetonide 4 mg twice a day and were followed monthly with serum PSA and cortisol levels. Those patients who had a greater than 25% increase in serum PSA from baseline at 2 months were considered to have progressive disease and were removed from study. Those patients who had a fall in serum PSA or stable disease were continued until disease progression. Bone scans were obtained every 12 weeks and at progression. Results: Twenty four patients with AIPC were treated between 11/02 and 6/04. A partial response with a >50% fall in serum PSA was seen in 29%. Another 21% achieved stable disease for a total response rate of 50%. There was no statistically significant difference in time to progression in the partial responders and stable disease patients. The median time to progression was 7.5 months. Treatment was well tolerated without any grade 3 or 4 toxicities. Patients with a higher degree of cortisol suppression appeared to have a better serum PSA response than those patients whose cortisol was less suppressed. Conclusion: Oral triamcinolone was well tolerated in patients with AIPC and good responses in serum PSA were observed in 50% of subjects. No significant financial relationships to disclose.
AMG 386, a selective angiopoietin 1/2-neutralizing peptibody, in combination with chemotherapy in adult patients with advanced solid tumors
Authors: A. C. Mita, D. Wang, C. H. Takimoto, E. Malseed, L. Nguyen, E. Rasmussen, C. Storgard, P. LoRusso
Journal: Journal of Clinical Oncology (2007)

14033 Introduction: AMG 386 is a selective angiopoietin 1 /2-neutralizing peptibody that inhibits angiogenesis by preventing interaction between angiopoietins and Tie2 receptors. This open-label study evaluated the safety, pharmacokinetics (PK), and antitumor activity of AMG 386 in combination with FOLFOX-4 (F), carboplatin + paclitaxel (CP), or docetaxel (D) in adult patients (pts) with advanced solid tumors. Methods: Three cohorts of 6–9 pts received 1 full cycle of chemotherapy (2 weeks of F or 3 weeks of D 75 mg/m 2 or CP). Administration of AMG 386 10 mg/kg IV weekly was started on day 1 of cycle 2 for patients who did not experience a dose-limiting toxicity (DLT) to chemotherapy during cycle 1, and continued until disease progression or intolerance. Safety and tolerability, tumor response (RECIST every 8 weeks), PK profiles of AMG 386 and chemotherapy agents, and formation of antibodies to AMG 386 were assessed. Results: As of October 2, 2006, 16 pts have received AMG 386: 6 pts in the F cohort, 5 in CP, and 5 in D; 7 pts were men, median age 59.5 years (range, 44- 75 years). No AMG 386-related serious AEs or DLTs were reported. AEs related to chemotherapy + AMG 386 in = 2 pts were neutropenia (n = 3), thrombocytopenia (n=2), diarrhea (n=2), and vomiting (n=2). No neutralizing antibodies were observed. F, CP, and D coadministered with AMG 386 did not appear to affect the PK profile of AMG 386, and AMG 386 had no apparent effect on the PK profile of 5 FU, leucovorin, C, P, or D. Tumor response data are available for 6 pts. One pt receiving CP+ AMG 386 for bladder cancer refractory to gemcitabine/cisplatin had a complete response (CR) at week 8, confirmed at week 16. Stable disease in 4 pts and progressive disease in 1 pt were also observed. Conclusions: Weekly administration of AMG 386 in combination with F, CP, or D appears to be safe and well tolerated. A CR in bladder cancer suggests promising antitumor activity of AMG 386 in combination with chemotherapy. Further clinical studies of AMG 386 in combination with chemotherapy and other targeted agents are warranted. [Table: see text]
Prediction of Tumor Radiosensitivity by Hexafluoromisonidazole Retention Monitored by [<sup>1</sup>H]/[<sup>19</sup>F] Magnetic Resonance Spectroscopy
Authors: Shi-Jiang Li, Guan-Yuan Jin, John E. Moulder
Journal: Cancer Communications (1991)

Hexafluoromisonidazole (CCI-103F) is a hypoxic cell label that can be measured by in vivo [1H]/[19F] magnetic resonance spectroscopy (MRS). The retention of CCI-103F in SCCVII tumors was found to be correlated with tumor size, with larger tumors retaining more label. Such a correlation was anticipated, as larger SCCVII tumors have larger hypoxic fractions. A significant but less strong correlation was also found between CCI-103F retention and the fraction of tumor cells surviving after 10 Gy irradiation, with tumors that retained larger amounts of CCI-103F having higher surviving fractions. These results indicated that non-invasive MRS measurement of CCI-103F retention could predict radiosensitivity in SCCVII tumors. The lack of a strong correlation between CCI-103F retention and radiosensitivity, however, indicated that hypoxic fraction was not the only factor influencing radiosensitivity in these tumors.
Analysis of Relapse Biopsies in Classical Hodgkin Lymphoma Reveals Correlations with Outcome after Autologous Stem Cell Transplantation
Authors: Fong Chun Chan, Anja Mottok, Alina S. Gerrie, Maryse M. Power, Kerry J. Savage, Joseph M. Connors, Randy D. Gascoyne, Sohrab P. Shah, David W. Scott, Christian Steidl
Journal: Blood (2014)
Prognostic Implications of the Differentiation Inhibitory Factornm23-H1 Protein in the Plasma of Aggressive Non-Hodgkin’s Lymphoma
Authors: Nozomi Niitsu, Junko Okabe-Kado, Takashi Kasukabe, Yuri Yamamoto-Yamaguchi, Masanori Umeda, Yoshio Honma
Journal: Blood (1999)
Vitamin D deficiency: A threat to bone health in breast cancer patients during adjuvant treatment with aromatase inhibitors
Authors: P. Lonning, J. Geisler, L. E. Krag, E. Løkkevik, T. Risberg, A. I. Hagen, E. Schlichting, G. E. Eide, E. Di Salle
Journal: Journal of Clinical Oncology (2006)

554 Background: To evaluate potential detrimental effects of the aromatase inactivator exemestane on bone, 147 postmenopausal women with early breast cancer were randomised to receive either exemestane for 2 years or placebo (J. Clin. Oncol. 23 [22], 5126–5137, 2005). Exemestane increased the annual bone loss from the femoral neck (2.72%) compared to placebo (1.48%; P = 0.024) with a non-significant increase in the lumbar spine (exemestane 2.17% versus placebo 1.84%). The annual bone loss was higher than expected in the placebo arm. Methods: Various biomarkers involved in bone metabolism (25-hydroxyvitamin D, parathormone, calcium, estrogens, androgens) were analysed to elucidate their influence on bone status at baseline and BMD loss during treatment with exemestane compared to placebo. Results: Using a cut-off value of 30 ng/ml for 25-hydroxyvitamin D (J. Clin. Endocrinol. Metab. 90 [6], 3800–3801, 2005), the majority of study participants suffered from vitamin D deficiency (56 of 62 patients in the placebo group and 52 of 59 in the exemestane group). The mean levels (95% confidence interval) of vitamin D were 22.6 ng/ml (21.2 - 24.1) in the placebo group and 21.6 ng/ml (20.0 - 23.3) in the treatment group, revealing no differences between these groups. Low serum calcium levels at baseline were found to be significantly correlated to low BMD in the femoral neck in the exemestane group. However, individual levels of vitamin D, parathormone and estradiol at baseline were not correlated significantly to BMD. Conclusions: Considering an annual bone loss of 0.5% to be representative for postmenopausal women (Osteoporos. Int. 15, 881–886, 2004), our data indicate that vitamin D deficiency could be the most important factor elevating bone loss among patients treated with exemestane as well as in the placebo group. These findings, together with the observation of a moderate additional effect of exemestane on bone loss, underlines the need for proper vitamin D substitution of postmenopausal women in general and in breast cancer patients during treatment with aromatase inhibitors in particular. [Table: see text]
Abstract 11731: Impact of Fasting Plasma Glucagon-like Peptide-1 Levels and Tissue Characteristics of Coronary Plaque in Patients with Coronary Artery Disease
Authors: Takayuki Mitsuhashi, Kiyoshi Hibi, Fumiyuki Otsuka, Masaaki Konishi, Kenichiro Saka, Nobuhiko Maejima, Mitsuaki Endo, Tsutomu Endo, Kazuo Kimura
Journal: Circulation (2012)

Background: Incretin is a gut-derived peptide and one of the enhancers of insulin secretion. Previous studies have reported that a major incretin, glucagon-like peptide-1 (GLP-1), is decreased in p...
<i>FLT3</i>Inhibitor–Associated Neutrophilic Dermatoses
Authors: Nisha Varadarajan, Andrea Boni, David E. Elder, Adam Bagg, Robert Micheletti, Alexander E. Perl, Misha Rosenbach
Journal: JAMA Dermatology (2016)

FLT3 Inhibitor-Associated Neutrophilic DermatosesAcute myeloid leukemia (AML) is a hematologic malignancy characterized by a disruption in normal hematopoiesis that results in uninhibited myeloblast proliferation.Cutaneous reactions in AML include leukemia cutis, Sweet syndrome, infections, and treatment-related effects.We present 3 cases of FLT3 (OMIM 136351) inhibitor-associated neutrophilic dermatoses (Table ).
MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines
Authors: Massimo Filippi, Maria A Rocca, Olga Ciccarelli, Nicola De Stefano, Nikos Evangelou, Ludwig Kappos, Alex Rovira, Jaume Sastre-Garriga, Mar Tintorè, Jette L Frederiksen, Claudio Gasperini, Jacqueline Palace, Daniel S Reich, Brenda Banwell, Xavier Montalban, Frederik Barkhof
Journal: The Lancet Neurology (2016)
Harms of Breast Cancer Screening: Systematic Review to Update the 2009 U.S. Preventive Services Task Force Recommendation
Authors: Heidi D. Nelson, Miranda Pappas, Amy Cantor, Jessica Griffin, Monica Daeges, Linda Humphrey
Journal: Annals of Internal Medicine (2016)

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: In 2009, the U.S. Preventive Services Task Force recommended biennial mammography screening for women aged 50 to 74 years and selective screening for those aged 40 to 49 years. Purpose: To review studies of screening in average-risk women with mammography, magnetic resonance imaging, or ultrasonography that reported on false-positive results, overdiagnosis, anxiety, pain, and radiation exposure. Data Sources: MEDLINE and Cochrane databases through December 2014. Study Selection: English-language systematic reviews, randomized trials, and observational studies of screening. Data Extraction: Investigators extracted and confirmed data from studies and dual-rated study quality. Discrepancies were resolved through consensus. Data Synthesis: Based on 2 studies of U.S. data, 10-year cumulative rates of false-positive mammography results and biopsies were higher with annual than biennial screening (61% vs. 42% and 7% vs. 5%, respectively) and for women aged 40 to 49 years, those with dense breasts, and those using combination hormone therapy. Twenty-nine studies using different methods reported overdiagnosis rates of 0% to 54%; rates from randomized trials were 11% to 22%. Women with false-positive results reported more anxiety, distress, and breast cancer–specific worry, although results varied across 80 observational studies. Thirty-nine observational studies indicated that some women reported pain during mammography (1% to 77%); of these, 11% to 46% declined future screening. Models estimated 2 to 11 screening-related deaths from radiation-induced cancer per 100 000 women using digital mammography, depending on age and screening interval. Five observational studies of tomosynthesis and mammography indicated increased biopsies but reduced recalls compared with mammography alone. Limitations: Studies of overdiagnosis were highly heterogeneous, and estimates varied depending on the analytic approach. Studies of anxiety and pain used different outcome measures. Radiation exposure was based on models. Conclusion: False-positive results are common and are higher for annual screening, younger women, and women with dense breasts. Although overdiagnosis, anxiety, pain, and radiation exposure may cause harm, their effects on individual women are difficult to estimate and vary widely. Primary Funding Source: Agency for Healthcare Research and Quality.
The use of PET scans in the management of non-small cell lung cancer patients relative to evidence-based indications across Canada.
Authors: Heather E. Bryant, Rami Rahal
Journal: Journal of Clinical Oncology (2013)

104 Background: PET scans are playing an increasingly important role in the management of cancer patients, particularly those diagnosed with non-small cell lung cancer (NSCLC). At the same time, the high capital and operating costs of the technology in the publicly funded Canadian health care system presents a strong case for monitoring use of PET scans relative to evidence based indications. This study by the Canadian Partnership Against Cancer reports on the use of PET scans in the management on NSCLC across Canada. Methods: PET scan utilization data from all hospitals providing the service in six Canadian provinces was linked to provincial cancer registry data, which allowed for the identification of demographic, diagnostic/prognostic, and treatment information on each NSCLC patient receiving a PET scan. The indication for each scan was then inferred from the timing of the scan relative to the dates of diagnosis, neoadjuvant therapy, surgery, curative chemo-radiation, or palliative treatment, as relevant for each patient’s care pathway. This way, the scan indications were identified as one of the following: staging, treatment planning, assessing treatment response during active treatment, and assessing metastases following end of curative treatment or palliative treatment. Results: The study results were not yet available at the time of submission of this abstract. Preliminary results and analyses will be available by the November 1, 2013, conference date. The results will include the following indicators for the 2009-2011 timeframe: percentage of NSCLC cases receiving a PET scan by stage; percentage NSCLC PET scans that are performed for each of the identified indications (diagnosis/staging, treatment planning, treatment response, follow up) by stage at diagnosis; variations by province, age group, and sex. Conclusions: This work will identify patterns in the use of PET scans for NSCLC patients across Canada and assess the extent to which this use is consistent with currently supported evidence based indications. The results will help inform more evidence-based use of the diagnostic technology across Canada and will form a baseline for future monitoring as the evidence evolves.
Validating a local failure risk stratification for use in a prospective study of adjuvant radiation in bladder cancer.
Authors: Brian C. Baumann, Jiwei He, Wei-Ting Hwang, Kai Tucker, Justin E. Bekelman, Harry W. Herr, Seth P. Lerner, Catherine M. Tangen, Thomas J. Guzzo, S. Bruce Malkowicz, John Paul Christodouleas
Journal: Journal of Clinical Oncology (2015)

347 Background: To inform the design of trials of adjuvant radiation (RT) for bladder cancer, a local failure (LF) risk grouping has been proposed and externally validated that stratifies radical cystectomy (RC) pts into 3 groups based on pathologic factors. This stratification was developed using historical surgical databases and may not reflect outcomes in the observation arm of a modern trial. The purpose of the study is to assess whether trial accrual bias or improving surgical techniques over time impact the validity of the stratification or reduce the LF risk estimates for each subgroup. Methods: The LF stratification was developed using 2 cohorts treated with RC +/- chemo: a single-institution cohort of 442 pts (1990-2008) and the multi-center SWOG 8710 cohort of 264 pts (1987-1998). To assess the impact of trial accrual bias, we excluded pts who developed LF, DM, died, or were lost to follow up &lt;90 days from surgery or completing post-op chemo as these pts are very unlikely to be enrolled in an adjuvant RT trial. 3-yr LF rates were estimated using Gray’s test. The stratification was considered valid if all 3 risk groups had significantly different LF rates. To assess the impact of improving surgical techniques over time, a Fine-Gray regression estimated the association of LF and year of RC while controlling for risk group. Results: Using the stricter criteria, 10% of SWOG pts and 14% from the other cohort were excluded. Analysis of the remaining pts confirmed 3 subgroups with significantly different LF risk: low risk (stage ≤pT2), intermediate risk (≥pT3 with negative margins and ≥10 nodes identified at surgery), and high risk (≥pT3 with positive margins OR &lt;10 nodes identified) with 3-yr LF rates of 7%, 17%, and 36%, respectively (p&lt;0.01), nearly identical to the rates when not accounting for accrual bias. Year of RC was not associated with LF risk on univariate analysis or after controlling for risk group in the SWOG, single-institution, or combined cohorts. Conclusions: These results suggest that neither trial accrual bias nor improvements in surgical techniques over time invalidate the LF risk stratification or substantially affect LF estimates. The proposed stratification is promising for use in adjuvant RT trials.