tbuckley/cabot-search huggingface dataset:
Multiplex genotyping and gene expression assays for colorectal cancer treatment selection markers
Authors: S. Y. Kwok, W. Kim, S. Tom, C. Christopherson, D. Wolfson, T. Toombs, S. Broder, J. Sninsky
Journal: Journal of Clinical Oncology (2005)

3651 Background: Molecular markers that predict inherent resistance or sensitivity to chemotherapy would greatly assist oncologists in selecting drugs with the best therapeutic index. Genetic alterations in TP, TS, DPD, UGT1A1,ERCC1, ERCC2 and GSTP1 have been reported to predict response of colorectal cancer (CRC) to 5FU, irinotecan and oxaliplatin as have the expression levels of some of these markers. Additionally, the increasing use of Avastin and Erbitux in CRC treatment suggests that further studies of VEGF and EGFR may also be warranted. Methods: Two multiplex TaqMan panels have been developed to simultaneously quantify expression of a) TS, TP, DPD and b) EGFR, ERCC1, VEGF. A novel housekeeping gene, NUP214, is incorporated into each panel and is used to normalize expression of the other genes. Each TaqMan probe within a panel is labeled with a different fluorescent reporter molecule that is readily differentiated. The multiplex genotyping assay simultaneously amplifies 6 SNPs, 2 repeat sequences and 1 ins/del. Genotyping of the SNPs is accomplished post-PCR with an oligonucleotide ligation assay (OLA) that uses fluorescent-labeled probes. The repeats and ins/dels are amplified with fluorescent-labeled primers and detected directly after PCR. Products of the PCR and the ligation assays are identified by specific fragment lengths on the ABI Prism 3100. Results: The TaqMan assays simultaneously quantifies each of the 6 targeted genes and the expression levels are normalized to NUP214. The assays have been successfully used on RNA extracted from colorectal FFPE. The genotyping assays show that the 6 SNPs can be simultaneously amplified and detected by OLA. The genotypes determined by this approach showed 100% concordance with individual allele-specific genotyping assays. Conclusions: The multiplex assays allow several markers to be interrogated simultaneously and for some genes, provide direct comparison of genotyping and gene expression results from the same tissue. These assays will aid in assessing the predictive value of these markers for CRC treatment and should contribute to improved patient management. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celera Diagnostics, Celera Genomics Celera Diagnostics, Celera Genomics Celera Diagnostics, Celera Genomics Celera Celera Celera Celera
A phase II study of Xcellerated T Cells in patients with relapsed or refractory indolent non-Hodgkin’s lymphoma (NHL)
Authors: J. G. Gribben, J. J. Stephenson, N. L. Bartlett, M. S. Milder, R. V. Boccia, C. Redfern, V. M. Mizuno, J. Hillson, R. J. Berenson, M. W. Frohlich
Journal: Journal of Clinical Oncology (2005)

2510 Background: Infusion of activated & expanded autologous T lymphocytes (Xcellerated T Cells [XTC]) leads to reduction in lymphadenopathy and splenomegaly in chronic lymphocytic leukemia (Castro et al., ASH 2004). The present study was designed to determine potential treatment effects in indolent NHL. Methods: 25 of 40 planned pts with small lymphocytic (SLL, n=9), mantle cell (MCL, n=4), marginal zone (MZL, n=2) & follicular cell (FCL, n=10) lymphoma have been enrolled to date. Median # prior treatment regimens was 2 (range 1–6). Peripheral blood mononuclear cells were collected by leukapheresis & activated/expanded ex vivo by incubation with anti-CD3 & anti-CD28 antibody-coated magnetic beads (Xcyte Dynabeads). The median total # cells available for infusion was 77.1 x 109 (range: 57.8–98.9; n=21), which were 98.5% ± 0.5% CD3+ (mean ± SD). Pts received 2 infusions of XTC (without any other therapy) separated by 6–8 weeks, & were evaluated every ∼6 wks. Results: Data from the 1st evaluation (prior to 2nd infusion) were available for 8 pts: 1 had unconfirmed complete response (CR) pending bone marrow exam (MZL). 3 of 4 SLL pts had marked reductions in peripheral lymphadenopathy by exam. Reduction in lymph node area was confirmed by CT scan in 2 pts, but did not meet criteria for radiographic response. Bone marrow in one SLL pt showed a decrease in leukemic involvement from 70% to 40%. In 2 SLL pts who have had 2nd & 3rd evaluations respectively, further reductions in lymph nodes were seen by CT scan, but have not reached criteria for response. 1 pt progressed (FCL) & 2 (MCL) were stable at 1st evaluation. An additional 3 pts (2 MCL, 1 FCL) progressed prior to any evaluation. Sustained increases in T cell counts were observed in all pts. Infusions were well-tolerated, & no serious adverse events related to therapy were reported. Conclusions: XTC could be manufactured in pts with indolent NHL. Infusion was well-tolerated & led to sustained increases in T cell counts and reductions in lymphadenopathy, including 1 pt with an unconfirmed CR. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Xcyte Therapies Xcyte Therapies
A checklist to facilitate objective hypothesis testing in social psychology research
Authors: Anthony N Washburn, G Scott Morgan, Linda J Skitka
Journal: Behavioral and Brain Sciences (2015)

Abstract Social psychology is not a very politically diverse area of inquiry, something that could negatively affect the objectivity of social psychological theory and research, as Duarte et al. argue in the target article. This commentary offers a number of checks to help researchers uncover possible biases and identify when they are engaging in hypothesis confirmation and advocacy instead of hypothesis testing.
Eugynon 30 and dermatitis. [Letter]
Authors: Morris Df
Journal: BMJ (1974)

In 1967; 1972 and 1974 Lyndiol-2.5; Norinyl-1; and Microgynon 30 were respectively prescribed to a woman who after taking a few tablets on each occasion developed a mild diffuse urticarial rash mostly on the limbs and chest.  She took the 1st 2 drugs for only 2 weeks but completed the course of Microgynon 30.  The rash disappeared during the pill-free week.  Piriton 4 mg was prescribed with the 2nd pill cycle to determine if it would modify the effect; it did not and the woman discontinued the pill on the 5th day.  She 1st conceived in 1957 and was found to be allergic to nickel; she had uneventful pregnancies in 1961 and 1967.  These oral contraceptives do not have any common hormone; dye; nor manufacturer and the problem has yet to be resolved.
The Oral Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) Demonstrates Broad and Durable Clinical Activity in Relapsed / Refractory Non Hodgkin’s Lymphoma (NHL)
Authors: John Kuruvilla, John C. Byrd, Joseph M Flynn, Ramiro Garzon, Pierluigi Porcu, Nina Wagner-Johnston, Mary Lynn Savoie, Richard M. Stone, Eric D. Jacobsen, Morten Mau-Sorensen, Peter de Nully Brown, Rachid Baz, Bijal Shal, Ian Flinn, Nashat Gabrail, Vishal Kukreti, Rodger E. Tiedemann, Yosef Landesman, Boris Klebanov, Eran Shacham, Jean-Richard Saint-Martin, Tracey Marshall, John McCartney, Dilara McCauley, Robert Carlson, Sasha Norori, Michael R Savona, Tami Rashal, Mansoor R Mirza, Michael Kauffman, Sharon Shacham
Journal: Blood (2014)
A phase II trial of trastuzumab (H) + capecitabine (X) as first-line treatment in patients (pts) with HER2-positive metastatic breast cancer (MBC)
Authors: L. Xu, S. Song, J. Zhu, R. Luo, L. Li, S. Jiao, L. Chen, M. Tao, Y. Su, D. Liu
Journal: Journal of Clinical Oncology (2006)

10615 Background: The addition of H to a taxane provides significant clinical benefit, including prolonged survival, in HER2-positive MBC. H adds little to the toxicity of taxanes alone. As monotherapy, X has consistently high activity and favorable safety. The addition of X to docetaxel extends survival in MBC. Preliminary data [Bangemann et al. 2000] indicated that the combination of H + X is effective and well-tolerated for intensively pretreated HER2-positive MBC (ORR 47%). The current study evaluated the efficacy and safety of H + X in first-line MBC. Methods: 72 pts of a planned population of 100 pts were enrolled between Mar03 and Dec05. All pts had measurable (WHO criteria), HER2-positive (IHC 3+ or IHC 2+/FISH positive) and untreated MBC, KPS ≥60, and adequate organ function. H was administered as a 4mg/kg loading dose followed by 2mg/kg i.v. weekly (until disease progression) and X 1250mg/m 2 bid d1–14 q3w (max 6 cycles). The primary endpoint was progression-free survival (PFS). Results: Baseline characteristics: median age 49 years (range 27–74), median KPS 90 (range 60–100). Principal tumor sites: lymph nodes (49%), lung (33%), liver (28%), breast (14%), thoracic wall (9%), chest (9%), other (12%). Prior treatment: surgery (77%), radiotherapy (21%), and adjuvant chemotherapy (58%), including anthracycline (35%), paclitaxel (7%), docetaxel (7%) and other (21%). 43 pts are evaluable for safety and efficacy. The remaining 29 pts are being analyzed. 6 pts received 3 cycles of H + X; the other 37 pts completed 6 cycles of treatment. 16 pts received H monotherapy after completing 6 cycles of H + X. 3 pts discontinued H due to disease progression. The most common grade 1/2 adverse events (AEs) were HFS (14%), neutropenia (14%), SGOT abnormality (16%), and SGPT abnormality (14%). Grade 3 HFS occurred in 4 pts (10%) with grade 3 myelosuppression in 1 pt (2%). AEs were mild and resolved in all pts. The overall response rate was 63%, including 5 CRs and 22 PRs. At a median follow-up of 6 months, median PFS has not been reached. Conclusions: The combination of H and X is a highly active and well-tolerated regimen for first-line treatment of HER2-positive MBC. Updated data will be presented. No significant financial relationships to disclose.
Quality-of-life outcomes of patients with breast cancer in an integrative cancer treatment setting.
Authors: E. D. Staren, D. Gupta, D. P. Braun
Journal: Journal of Clinical Oncology (2010)

1107 Background: There is evidence in the literature to suggest that patients undergoing cancer therapy experience an initial deterioration in their quality of life (QoL). We longitudinally investigated the impact of an integrative care model characterized by conventional cancer treatment in combination with a comprehensive, complementary program on QoL outcomes of patients with breast cancer. Methods: We examined a random sample of 689 breast cancer patients treated at two single-system cancer centers from January 2001 to December 2008 who were available for a minimum follow-up of 3 months. QoL was evaluated using the validated survey instrument European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) at baseline and after 3 months of treatment. The QLQ-C30 provides a global score as well as five functional and nine symptom scores. Higher scores in the global and functional scales and lower scores in the symptom scales indicate better QoL. The mean QoL scores were compared using paired sample t-test. Results: QoL scores for all patients together were well maintained from baseline to 3 months for both global scores (63.6 vs. 61.7, p=0.11) and across scales, excluding emotional functioning (66.6 vs. 71.3, p<0.001) and insomnia (36.7 vs. 32, p=0.003), both of which actually improved at 3 months. There were 257 analytic and 432 non-analytic patients whose mean global QoL scores were 67 and 61.5 at baseline (p=0.005) and 65 and 59.7 at 3 months (p=0.006). There was no significant difference in mean global scores at baseline as compared with 3 months for either analytic or non-analytic patients. Patient's stage of disease at diagnosis was I, 133; II, 282; III, 145; and IV, 85. Mean global QoL scores for locoregional (stages I-III) and metastatic (stage IV) disease patients were 63.4 and 65.2 at baseline (p=0.53) and 61.9 and 59.8 at 3 months (p=0.45); there was no significant difference in mean global scores at baseline as compared with 3 months for either loco-regional or metastatic disease patients. Conclusions: This study suggests that the QoL outcomes of patients with breast cancer are maintained and may even be improved while undergoing therapy in an integrative cancer treatment setting. No significant financial relationships to disclose.
<i>MYD88</i>L265P Mutations, But No Other Variants, Identify a Subpopulation of DLBCL Patients of Activated B-cell Origin, Extranodal Involvement, and Poor Outcome
Authors: Jordina Rovira, Kennosuke Karube, Alexandra Valera, Dolors Colomer, Anna Enjuanes, Lluís Colomo, Alejandra Martínez-Trillos, Eva Giné, Ivan Dlouhy, Laura Magnano, Julio Delgado, Antonio Martínez, Neus Villamor, Elías Campo, Armando López-Guillermo
Journal: Clinical Cancer Research (2016)

Mutations in MYD88 are found in different lymphoproliferative disorders associated with particular biologic characteristics and clinical impact. The aim of this study was to analyze the incidence of MYD88 mutations and its clinical impact in diffuse large B-cell lymphoma (DLBCL).The incidence, clinicobiological features, and outcome of 213 patients (115 M/98 F; median age, 65 years) with DLBCL treated with immunochemotherapy in a single institution according to MYD88 mutational status as assessed by an allele-specific PCR assay were analyzed. The cell of origin (COO) was determined in 129 cases by gene expression.MYD88 mutations were found in 47 cases (22%), including L265P in 39 and S219C and M232F in 4 cases, respectively. Patients with MYD88 L265P were older, presenting frequent extranodal involvement, and mostly corresponded to activated B-cell like (ABC) subtype, whereas no preference in COO was observed in patients with other MYD88 mutations. Five-year overall survival (OS) for MYD88 wild-type, MYD88 L265P, and other variants was 62%, 52%, and 75%, respectively (P = 0.05). International Prognostic Index (IPI) (HR, 2.71; P < 0.001) and MYD88 L265P (HR, 1.786; P = 0.023) were independent variables predicting OS in the multivariate analysis. However, MYD88 L265P lost its independent value when COO was included in the model.Our findings indicate that MYD88 L265P mutations, but no other variants, identify a subgroup of DLBCL mainly of ABC origin, with extranodal involvement and poor outcome. Clin Cancer Res; 22(11); 2755-64. ©2016 AACR.
Imatinib in the treatment of tenosynovial giant-cell tumor and pigmented villonodular synovitis.
Authors: V. Ravi, W. Wang, D. M. Araujo, J. A. Ludwig, R. J. Luke, V. O. Lewis, J. C. Trent, R. S. Benjamin, S. Patel
Journal: Journal of Clinical Oncology (2010)

10011 Background: Tenosynovial giant-cell tumor (TGCT) and pigmented villonodular synovitis (PVNS) are clonal neoplastic proliferations arising from the synovium producing pain, swelling and limitation of movement in the affected joint. Most cases of TGCT/PVNS have translocations involving CSF1 located at 1p13. The fusion protein recruits non-neoplastic cells that express CSF1R through a paracrine effect. Imatinib has been shown to inhibit CSF1R and induce tumor regression in a patient with unresectable PVNS. We present a series of 6 patients with TGCT/PVNS treated with imatinib at our institution. Methods: Between June 2008 and December 2009, 6 patients with recurrent or unresectable PVNS/TGCT were treated with imatinib at M. D. Anderson Cancer Center. Imatinib was dosed at 400 mg daily in all cases. Patients were evaluated for response to therapy both clinically (improvement in function, decrease in pain and swelling) and using imaging studies (MRI and/or FDG-PET). Results: 5/6 patients (83%) showed improvement in pain, swelling or joint function. FDG-PET scans were performed on 2 patients, one patient was imaged as early as 2 weeks showing a decrease in FDG uptake while the other patient was imaged at 6 weeks showing a 75% decrease in SUVmax. MRI showed decrease in size of the lesion and contrast enhancement in 3/6 (50%) patients. Stable disease was observed in 2/6 (33%) patients. Treatment was discontinued in 2 patients, one with stable disease (due to financial reasons) and the other with a partial response (due to drug toxicity). Both patients showed progression after discontinuation of imatinib. 2 patients underwent surgery following therapy with imatinib and remain disease free at 16 months and 5.5 months of follow-up. Imatinib was not continued postoperatively in these patients. Conclusions: Imatinib shows promising activity in TGCT/PVNS and warrants further evaluation in a prospective clinical trial. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Prognostic Factors of Elderly Patients with Acute Myeloid Leukemia: a Retrospective Multi-Center Study on 101 Patients
Authors: Shinichi Ogawa, Masanori Seki, Tatsuhiro Sakamoto, Yasuhisa Yokoyama, Naoki Kurita, Naoshi Obara, Daisuke Kudo, Atsushi Shinagawa, Yuichi Hasegawa, Shigeru Chiba
Journal: Annals of Oncology (2014)
Comparing Disease Outcome of Women with Hormone Receptor-Negative/Her2-Positive (Hr-/Her2+) or Triple Negative (Tn) Metastatic Breast Cancer (Mbc) Receiving Multiple Lines of Chemotherapy: a Mono-Institutional Retrospective Analysis
Authors: F. Sottotetti, R. Palumbo, A. Riccardi, E. Quaquarini, C.M. Teragni, B. Tagliaferri, E. Pozzi, A. Bernardo
Journal: Annals of Oncology (2014)
4F2, a novel marker for grade of malignancy in renal cell cancer (RCC)
Authors: M. Pöttler, None Kalinowska, M. Susani, A. Haitel, None Zielinski, None G
Journal: Journal of Clinical Oncology (2008)

22148 The transmembrane protein 4F2 (CD98) is essential in embryogenesis as well as in adolescence during cell proliferation, while in quiescent somatic cells 4F2 is not expressed. Although in certain tumors 4F2 expression has been described, qualitative or quantitative correlation of 4F2 expression and tumor behavior is so far not studied. In this study we performed immunohistochemical analyses of clear-cell renal cell cancer (ccRCC) as well as papillary renal cell cancer (pRCC) on paraffin-embedded tumors from a tissue bank of the Department of Clinical Pathology (Med.Uni.Vienna). Renal cell carcinomas were derived from primary tumors with different grading and are classified according to the recommendations of the WHO Classification 2004, staged according to the TNM-System (Sobin LH. Int. 2002), and graded according to Fuhrman et al (Am J Surg Pathol, 1982). None of the patients had been treated with chemotherapy prior to surgery. 4F2 stained tumor slides were co-stained with established tumor type marker for ccRCC, CD10 as well as aquaporin-1, and for pRCC with cytocreatin 7 (CK7), a significant marker for Type I pRCC. Sections were scored using a semiquantitative scale for each individual tumor tissue sample, with - for negative staining, + to +++ 4F2 positive tumors, depending on the intensity of reaction. As threshold of 10% of cells showing immunoreactivity were set. For statistically analyses Tukey test was used and immunohistochemical scoring results, tumor type, grading and staging in carcinomas were compared. We found that 4F2 expression is almost exclusively found in the more aggressive Type II pRCC whereby the less aggressive type I did hardly show positive staining (93% type II, 4% type I, p <0.01, n=52). Consistently, in ccRCC multi tissue arrays we found a direct correlation between 4F2 expression and differentiation, whereby semiquantitative analyses showed highest stain in tumors of grade 3 and 4, n=120. From these data we conclude, that 4F2 expression statistically significant correlates with grade of differentiation. So far, renal cell cancer is patho-histological classified into grade of differentiation (Fuhrman et al), but an independent marker for grading has so far not described. In this study, we give clear evidence that 4F2 might act as a novel diagnostic marker in renal cell cancer. No significant financial relationships to disclose.
Abstract 18323: Positive Frequency-Dependent Effects of Highly Selective Kv1.5 Blockers (XEN-D0103 & MK-0448) in Right Atrial Trabeculae From Patients in Sinus Rhythm
Authors: Simone Loose, Judith MÜller, Erich Wettwer, Said El-Haou, Claire Jackson, Raymond Tang, James Milnes, Ursula Ravens, John Ford
Journal: Circulation (2013)

Aim: Despite promising effects of Kv1.5 blockers in experimental models of atrial fibrillation, limited data is available for man. Therefore we investigated two selective Kv1.5 channel blockers, XE...
Establishment of the image bank within the German COPD cohort COSYCONET
Authors: Bertram Jobst, Jürgen Biederer, Iven Fellhauer, Julia Schliebus, Annette Opgenorth, Claus-Peter Heussel, Hans-Ulrich Kauczor
Journal: European Respiratory Journal (2014)

Introduction : Imaging data play an increasing role in phenotyping and phenotype-genotype correlations of COPD with regard to an airway- or emphysema-type and additional subphenotypes. Within the COSYCONET cohort an image bank has been installed collecting all available chest CTs from the participants regardless of time of acquisition.

Methods : After pseudonymisation CT data underwent qualitative analysis: lobar-based assessment of presence or absence of abnormalities related to large or small airways and estimation of extent of emphysema. Quantitatively, emphysema was assessed by mean lung density, low attenuation area percent and 15 percentile; airways were assessed with regard to wall thickness and wall area percent.

Results : 412 CT data sets from 24 centers were collected until 12/2013. 86 % of the scans were less than 4 years old. The clinical indication was emphysema/COPD in 67 % of patients, nodule or lung cancer in 15 % and only 8 % for infiltrates. 40 % of scans were contrast-enhanced, which carries inherent difficulties for the quantitative analysis of emphysema. 55 % of the scans had a slice thickness of 3 mm or less, which is deemed adequate. Airway type is more frequent in lower GOLD stages, whereas emphysema extent gradually increases with GOLD stage.

Conclusions : The retrospective collection of CTs reflects the clinical reality in imaging COPD. It represents an important repository for phenotyping. Due to the shortcomings, a prospective study comparing MRI and CT for phenotyping COPD was initiated in a subcohort of COSYCONET in December 2013.

Supported by Competence Network Asthma/COPD, funded by FM of Education and Research, FKZ 01GI0884.