tbuckley/cabot-search huggingface dataset:
Serial Sequencing in Myelodysplastic Syndromes Reveals Dynamic Changes in Clonal Architecture and Allows for a New Prognostic Assessment of Mutations Detected in Cross-Sectional Testing
Authors: Hideki Makishima, Kenichi Yoshida, Thomas LaFramboise, Tetsuichi Yoshizato, Matthew Ruffalo, Mikkael A. Sekeres, Bartlomiej Przychodzen, Hiromichi Suzuki, Masashi Sanada, Yasunobu Nagata, Yusuke Okuno, Yusuke Sato, Aiko Sato-Otsubo, Michael J. Clemente, Naoko Hosono, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Yusuke Shiozawa, Ines Gomez-Segui, Holleh Husseinzadeh, Swapna Thota, Kathryn Guinta, Brittney Dienes, Tsuyoshi Nakamaki, Shuichi Miyawaki, Yogen Saunthararajah, Shigeru Chiba, Satoru Miyano, Lee-Yung Shih, Seishi Ogawa, Jaroslaw P. Maciejewski
Journal: Blood (2015)
Activity of the Histone Deacetylase Inhibitor, Vorinostat, Against BCR-ABL Positive Leukemia Cells with Random Mutagenesis and In Combination with Nilotinib
Authors: Seiichi Okabe, Tetsuzo Tauchi, Eishi Ashihara, Shinya Kimura, Taira Maekawa, Kazuma Ohyashiki
Journal: Blood (2010)
Assessing the Preparatory Grief in Advanced Cancer Patients (PGAC) instrument in an American population.
Authors: Maxwell Thomas Vergo, Jeremy D. Whyman, Jeanne Kestel, Christopher Rector
Journal: Journal of Clinical Oncology (2014)

225 Background: Only 50% of cancer patients who screen positive on the Distress Thermometer accept referral to psychosocial resources and mainly for challenges coping with overwhelming emotional response to losses. The Preparatory Grief in Advanced Cancer (PGAC) instrument was shown to have significant associations with hopelessness, anxiety, and depression in a Greek population with favorable potential as a screening tool. We aimed to assess the use of the PGAC in a sample of American patients diagnosed with incurable cancer as a more efficient screening tool for patients who would benefit from additional psychosocial referrals. Methods: We conducted this survey with participants from Northwestern University in Chicago, IL. Participants were US citizens and &gt;18 years old with an incurable cancer and no history of substance abuse or current psychiatric diagnosis. Patients were asked to complete a single survey composed of demographic data and scales including the PGAC, Distress Thermometer, HADS, ESAS and QOL. We used pair-wise correlation measurements, which included p-value measurements for testing whether the correlation coefficient was significantly different from 0. We then used pair-wise correlation coefficients to assess for p-value &lt; 0.05 at different PGAC scores. Results: 53 patients were surveyed, of which 57% (30) were outpatients. The PGAC score was associated with the distress thermometer (R=0.74, p=&lt;0.001), HADS (R=0.65, p=&lt;0.01), and ESAS (R=0.49, p=&lt;0.01) as well as inversely correlated with QOL score (R=-0.45, p=&lt;0.001). Additionally, PGAC &gt; 21 (p=0.02) was associated with elevated distress thermometer score (p=0.02) and elevated HADS scores (p=0.04). Conclusions: We tested the PGAC in an American population for the first time and found correlation between PGAC other validated measures (Distress Thermometer, ESAS, HADS, QOL) in an American population. We propose a PGAC cutoff of &gt;21 to assess for preparatory grief due to its association with elevated scores on Distress and HADS scales above this threshold. This instrument may better identify patients struggling with coping who would benefit from additional support but further investigation is needed.
BMP-4 production by bladder cancer cells favors tumor progression and promotes the development of a pro-tumoral immune environment
Authors: M. Dueñas, V. Martínez, F. López, M. Martínez, C. Rubio, C. Segovia, A. Teijeira, F. Villacampa, Á. Vicente, J. Paramio
Journal: Annals of Oncology (2016)
ALOX5 polymorphism and risk of colorectal polyps
Authors: Elizabeth M. Poole, Jeannette Bigler, John Whitton, John D. Potter, Justin G. Sibert, Cornelia M. Ulrich
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

758 

Introduction: Arachidonate 5-lipoxygenase (ALOX5) is important in the synthesis of leukotriene A4, an autocrine signaling molecule involved in host defense reactions and inflammation. ALOX5 has been described as a procarcinogenic lipoxygenase and is upregulated in colon cancer. In addition, ALOX5 acts on the same substrate as the COX-1 and -2 enzymes, potentially influencing the effects of these enzymes in colorectal carcinogenesis. A 6-base variable number tandem repeat (VNTR) polymorphism has been identified in the promoter region of ALOX5 . Having fewer repeats than the wildtype 5/5 repeats is associated with lower gene expression whereas the impact of more repeats is not clear. Methods: In a Minnesota-based case-control study of cases of adenomatous (n=524) and hyperplastic polyps (n=194), vs. polyp-free controls (n=622), we investigated the role of the ALOX5 VNTR polymorphism. Multivariable logistic regression analysis was used, controlling for the effects of age, sex, BMI, calories consumed, alcohol intake, fiber intake, hormone use, and smoking. Results: We observed alleles ranging from 2 to 8 repeats. The 5/5 genotype was most prevalent (61% among controls). For adenomatous polyps, having either fewer or more than 5 repeats was associated with a decreased risk of colorectal polyps relative to the 5/5 (wildtype) genotype ( 5: OR 0.70, 95% CI 0.33-1.47). Similar results were seen for hyperplastic polyps. The inverse association with aspirin or other NSAID use appeared stronger among those with fewer ALOX5 repeats ( 5). However this interaction was not statistically significant. Again, a similar pattern was seen among hyperplastic polyps. Conclusion: These results suggest that the ALOX5 promoter polymorphism does not significantly affect risk of colorectal polyps, but the association may depend on NSAID use. A possible risk reduction among individuals with fewer repeats - associated with reduced gene expression - is consistent with previous findings that ALOX5 is overexpressed in colorectal cancer tissue.



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Mepolizumab Significantly Improves Health Status and Asthma Control in Severe Eosinophilic Asthma: The Musca Study - a Phase IIIb Randomized, Placebo-Controlled Trial
Authors: Geoffrey L. Chupp, Eric S. Bradford, Frank C. Albers, Daniel J. Bratton, Jie Wang-Jairaj, Linda M. Nelsen, Jennifer L. Trevor, Antoine Magnan, Anneke ten Brinke
Journal: Journal of Allergy and Clinical Immunology (2017)
Clinical characteristics and natural history of patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (<i>EGFR</i>) mutations treated with erlotinib or gefitinib
Authors: G. J. Riely, V. A. Miller, W. Pao, M. Zakowski, M. Ladanyi, R. T. Heelan, M. G. Kris
Journal: Journal of Clinical Oncology (2005)

7085 Background: The EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib induce significant regressions and improve survival in patients with NSCLC. Mutations in the EGFR tyrosine kinase domain are associated with sensitivity to these drugs. As tumors with EGFR mutations are unique biologically, we undertook this project to identify the clinical characteristics and define the natural history of patients with NSCLC with EGFR mutations. We report data on the first 20 patients with EGFR mutations treated with EGFR TKIs at MSK. Methods: Patients with metastatic NSCLC treated with EGFR TKIs consented to analysis of tissue obtained prior to treatment. EGFR mutations were determined by direct sequencing or by non-sequencing-based PCR assays. EGFR mutation status for the tumor specimens in this analysis was previously reported (Pao et al PLoS Medicine, 2005). Results: EGFR mutations were identified in 20 patients. Exon 19 deletions: 11, exon 21 L858R point mutations: 9; gefitinib: 12, erlotinib: 8; Median Age: 67, Female/Male 45/55% (9/11); AdenoCa: 7, AdenoCa with bronchioloalveolar carcinoma (BAC) features: 9, BAC with focal invasion: 4; Never smokers: 55% (11/20). Former/current smokers smoked a median of 25 pack years. The median time from diagnosis to receiving EGFR TKI was 25 months (0–161 months). All (18/18; 100% observed rate, 95% CI 82–100%) patients with radiographically evaluable disease had a partial response. The median time to progression was 9.4 months (95% CI 8.4–28.8 months range: 3.3 months-28+ months). The median overall survival from start of EGFR TKI was 19.1 months (95% CI 13.8 months-not reached; range: 4 months-34+ months). The median survival of current/former smokers was 10.6 months and not reached (> 20 months) in never smokers (log rank p=0.03). Conclusions: All patients with NSCLC and EGFR mutations responded to erlotinib or gefitinib. These patients had a distinct clinical course with a median of 25 months to treatment with EGFR TKI and a median survival on these drugs of 19 months. Former/current smokers with EGFR mutations have a significantly shorter median survival than never smokers. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Genentech AstraZeneca AstraZeneca
Erratum: The association between cardiorespiratory fitness and impaired fasting glucose and type 2 diabetes mellitus in men (Annals of Internal Medicine (1999) 130 (89-96))
Authors: M. Wei, L. W. Gibbons, T. L. Mitchell, J. B. Kampert, C. D. Lee, S. N. Blair
Journal: Annals of Internal Medicine (1999)
Gender, age, and ethnic representation in non-small cell lung cancer (NSCLC) U.S. registration trials: FDA review.
Authors: S. M. Malik, A. T. Farrell, Q. Xu, R. Sridhara, R. Pazdur
Journal: Journal of Clinical Oncology (2011)

1530 Background: Lung cancer remains a leading cause of death in US. Despite decrease in the overall lung cancer death rates, the reports of disparity by gender, age and race persist. Surveillance, Epidemiology, and End Results (SEER Data) from 2003-2007 results show that of patients diagnosed with lung cancer approximately 58% are men and 42% are women, 31.6% are < 65, 68.4% are >= 65 years of age and that the median age at diagnosis is 71 years of age. The incidence rate is higher for African Americans (73.5 per 100,000) compared with that for Caucasians (63.8 per 100,000). We reviewed trial data submitted for FDA drug approvals for the treatment of NSCLC over the last decade to see if the trial population represented the US population who were to receive these drugs. Methods: We reviewed our NDA and BLA files for agents approved to treat NSCLC from January 2000-December 2010.Within those applications, we analyzed the gender, age, and ethnicity data from ten pivotal trials. Results: Ten national and international trials enrolled a total of 8795 patients, 6015 (68.4%) males and 2780 (31.6%) females. The age group enrolled less than 65 years of age was 5656 (64.3%) and 3131 (35.6%) for the group more than 65 years and approximate median age for all the trials was 60 years. Ethnicity results showed the enrollment of Caucasians 6892(78.4%), Asians 1325 (15%), Blacks 194 (2.2%), Hispanics 184 (2%) and other 200 (2.3%). Conclusions: Our results suggest that the trial population used for approvals do not represent well the US population who may receive the marketed agent. Women, Blacks, and the elderly were less frequently enrolled in trials. Disparity was especially pronounced in the age and ethnicity. This fact is concerning particularly for older patients who may experience greater toxicity when given the same dose and combination of drugs based on testing in younger population. The enrollment of Blacks was only 2.2%. Efforts should be made to encourage enrollment and participations in clinical trials by ethnic and racial minorities and older age group who are more prevalent to receive these therapies.
Gut Microbiota Composition of Non-IgE Mediated Cow's Milk Allergic Infants before and after Dietary Management with a Synbiotics-Supplemented Amino Acid-Based Formula
Authors: Harm Wopereis, Marleen Van Ampting, David C.A. Candy, Diego Peroni, Yvan Vandenplas, Adam Fox, Manon M. Oude Nijhuis, Lucien Harthoorn, Louise J. Michaelis, Jan Knol, Christina E. West
Journal: Journal of Allergy and Clinical Immunology (2017)
Granulocyte Colony-Stimulating Factor-Mediated Immunoregulation Via Inducing Blood Cells Expressing Human Leucocyte Antigen-G.
Authors: Hui Liu, Xuan Du, Yinkui Chen, Li Xuan, Xiuli Wu, Yu Zhang, Zhiping Fan, Fen Huang, Xian Zhang, Xiao Zhai, Fuhua Zhang, Jing Sun, Qifa Liu
Journal: Blood (2012)
Trends in treatment and survival for advanced pancreatic cancer: Progress or progression?
Authors: Mariam F. Eskander, Gyulnara G. Kasumova, Chun Li, Sing Chau Ng, Rebecca A. Miksad, Jennifer F. Tseng
Journal: Journal of Clinical Oncology (2016)

421 Background: There are increasing therapeutic options for patients with advanced pancreatic cancer but it is unknown whether the overall prognosis of unresectable patients is improving. Here, we examine trends in treatment and survival in Stage III/IV pancreatic cancer. Methods: National Cancer DataBase 1998-2012 queried for unresected pancreatic adenocarcinoma patients from Commission on Cancer hospitals with Stage III and IV disease. Trends in stage at diagnosis and type of chemotherapy (single vs. multi-agent) assessed via Cochran Armitage trend tests. Timing of treatment compared by Kruskal-Wallis. Kaplan-Meier analysis and Cox proportional hazards models used to assess the association between 2-year time intervals (1998-2011) and survival. Results: 34,163 unresected patients with Stage III and 100,396 with stage IV identified. Rates of chemotherapy increased over time for stage III (p&lt;0.0001) and stage IV (p&lt;0.0001). Among patients who received systemic therapy, rates of multiagent chemotherapy have increased for both stage III (p&lt;0.0001) and IV (p&lt;0.0001). Time from diagnosis to treatment did not change (p=0.5121). Overall survival differed by year group for stage III (5.2 mos in 1998-1999 vs. 9.0 mos 2010-2011, log-rank p&lt;0.0001) and stage IV (3.1 vs. 3.6 mos; log-rank p&lt;0.0001). Among patients who received chemotherapy, overall survival also differed (Stage III, 7.6 vs. 11.4 mos, log-rank p&lt;0.0001; Stage IV, 5.0 vs. 6.0 mos, log-rank p&lt;0.0001). After stratification by clinical stage, type of chemotherapy, tumor location, and facility type, year remained a significant predictor of survival (p&lt;0.0001). Conclusions: Survival of patients with Stage III and IV pancreatic cancer has significantly improved over the last fifteen years. This improvement in survival is not fully explained by changes in chemotherapy. [Table: see text]
A child with hyper-IgM syndrome and multiple endocrinopathies with mutations in signal transducer and activator 5B (STAT5B), phosphatidylinositol 3-kinase catalytic subunit delta (PIK3CD) and phosphatidylinositol 3-kinase regulatory subunit 1 (PIK3R1)
Authors: Miranda L. Curtiss, Maria Descartes, Bruce R. Korf, T. Prescott Atkinson
Journal: Journal of Allergy and Clinical Immunology (2017)
OS7.3 Impact of platelets and coagulation factors on the early steps of the brain metastatic cascade
Authors: M. J. Feinauer, A. S. Berghoff, G. Solecki, J. K. Grosch, A. T. Bauer, J. R. Arteta, M. Osswald, S. W. Schneider, W. Wick, F. Winkler
Journal: Neuro-Oncology (2016)
MicroRNA-based assay for differential diagnosis of mesothelioma
Authors: H. Benjamin, D. Lebanony, S. Tabak, N. Barabash, H. Gibori, S. Morgenstern, E. Meiri, Z. Bentwich, S. Rosenwald, D. Cohen
Journal: Journal of Clinical Oncology (2009)

e22079 Background: Malignant mesothelioma is an aggressive pleural neoplasm, strongly linked to environmental exposures such as asbestos. Mesothelioma can be difficult to differentiate from other tumors in the lung or pleura such as primary lung adenocarcinoma presenting with pleural effusion or metastatic adenocarcinoma from extrathoracic sites. We addressed the increasing need for accurate differential diagnosis of these tumors by developing a diagnostic assay based on expression levels of microRNAs, a family of small, non-coding RNAs whose tissue-specificity has proven applicability for identification of cancer tissue type and histology. Methods: We developed protocols for extraction of high-quality RNA that retain the microRNA fraction from FFPE tissue samples. Microarrays were used for initial profiling. qRT-PCR was used to validate results and to develop a diagnostic assay. Results: We identified microRNAs that are differentially expressed between mesothelioma, lung adenocarcinoma, and other confounding tumor types. A diagnostic assay (miRview™ meso) was developed, that utilizes qRT-PCR measurement of a small set of microRNAs to differentiate between mesothelioma and non-mesothelioma samples. After establishing this profile in more than 30 mesotheliomas and 200 samples of confounding tumors, the microRNA biomarkers were measured using a standardized protocol on a blinded test set. The assay had accuracy greater than 90% in differentiating mesothelioma from other confounding tumor types. More than ¾ of samples were classified with high confidence, and these samples were all correctly identified. Conclusions: MicroRNAs are emerging as effective cancer biomarkers. A robust and simple assay based on the expression level of a few microRNA biomarkers can accurately differentiate mesothelioma from other possible tumors in the lung and pleura. This assay provides an important new tool for diagnosing mesothelioma. [Table: see text]
Blockade of Costimulatory Signal Enhanced Glucocorticoid Suppression of T Cell-Induced Eosinophilia
Authors: Akio Mori, Satoshi Kouyama, Miyako Yamaguchi, Akemi Ohtomo-Abe, Yosuke Kamide, Hiroaki Hayashi, Kentaro Watai, Chihiro Mitsui, Kiyoshi Sekiya, Takahiro Tsuburai, Masami Taniguchi, Takayuki Ohtomo, Osamu Kaminuma
Journal: Journal of Allergy and Clinical Immunology (2017)
Breast cancer in Irish families with Lynch syndrome.
Authors: Emmet Jordan, Michael P. Farrell, Karen Anne Cadoo, R. M. Clarke, C. Nolan, M. R. Kell, John McCaffrey, Michael A. Maher, E. M. Connolly, Terence Boyle, M. John Kennedy, P. J. Morrison, C. Muldoon, David J Gallagher
Journal: Journal of Clinical Oncology (2012)

1543 Background: Breast cancer is not among the recognised malignant manifestations of Lynch Syndrome which include colorectal, endometrial, gastric, ovarian and upper urinary tract tumours. In this study we report the prevalence of breast cancer in Irish Lynch Syndrome families and determine immunohistochemical (IHC) expression of mismatch repair proteins (MMR) in available breast cancer tissue. Methods: Breast cancer prevalence was determined among Lynch Syndrome kindreds from two institutions in Ireland. One kindred was omitted due to a biallelic MMR and BRCA1 mutation.The clinicopathological data that was collected on breast cancer cases included age of onset, morphology, and hormone receptor status, and a genotype phenotype correlation was investigated. Immunohistochemical staining was performed for MLH1, MSH2, MSH6, and PMS2 on all available breast cancer tissue from affected individuals. Results: The distribution of MMR mutations seen in sixteen pedigrees were as follows; MLH1 (n=5), MSH2 (7), MSH6 (3), PMS2 (1). Sixty cases of colorectal cancer and 14 cases of endometrial cancer were seen. Seven breast cancers (5 invasive ductal and 2 invasive lobular cancers) and 1 case of ductal carcinoma in situ were reported in 7 pedigrees. This compared with 4 cases of prostate cancer. Of the 7 LS kindreds containing breast cancer, 6 MSH2 mutations and 1 MSH6 mutations were identified. Median age of breast cancer diagnosis was 49 years (range 38-57). Hormone receptor status is available on 3 breast cancer cases at time of abstract submission; all were ER positive and HER 2 negative. All cases had grade 2 or 3 tumours. 5 samples were available for IHC evaluation. 3 out of 5 cases showed loss of MMR expression, all showed loss of MSH2 and MSH6 expression. One of the two cases with normal IHC expression in breast tissue belonged to a kindred where 3 siblings with colorectal cancer and documented deleterious mutations demonstrated no IHC loss. Conclusions: Breast cancer occurred at an early age and was more common than prostate cancer in Irish Lynch Syndrome pedigrees. All identified breast cancer were in kindreds with MSH2 or MSH6 mutations. Enhanced breast cancer screening may be warranted in certain Lynch Syndrome kindreds.
Changes Identified by Flow Cytometry and WT1 Expression in Consecutive Bone Marrow Samples in Refractory Cytopenia of Childhood and Aplastic Anemia Before Start of the Therapy
Authors: Michaela Reiterova, Karolina Kramarzova, Martina Sukova, Vit Campr, Elena Vodickova, Ondrej Zapletal, Jan Blatny, Zuzana Zemanova, Libuse Lizcova, Vendula Pelkova, Jan Trka, Jan Stary, Ondrej Hrusak, Ester Mejstrikova
Journal: Blood (2011)
Neoadjuvant ipilimumab in locally/regionally advanced melanoma: Clinical outcome and biomarker analysis.
Authors: Ahmad A. Tarhini, Howard Edington, Lisa H. Butterfield, Yongli Shuai, Yan Lin, Uma N. Rao, John M. Kirkwood
Journal: Journal of Clinical Oncology (2012)

76 Background: Neoadjuvant ipilimumab (Ipi) for stage IIIB-C melanoma may improve the clinical outcome and provide access to pre/post Ipi blood. Methods: Pts were treated with Ipi (10mg/kg IV q3wks x 2 doses) bracketing definitive surgery. Tissue samples were obtained at baseline and at surgery (wk ≥ 6) and serum/PBMC collected at baseline, 6 wks, 3, 6, 9, 12 mos and/or progression. Flow cytometry was used to monitor the host immune response in blood and evaluable tumor. IHC for select markers was also performed. Baseline and wk-6 serum cytokines were tested by xMAP multiplex technology (Luminex Corp). Results: 31 pts were enrolled, 6 had stage IIIB (N2b, N2c), and 25 IIIC (N3) melanoma. Worst toxicities (N=31 pts) included grade 3 diarrhea/colitis (5 pts; 16%), hepatitis (2; 6%), rash (1; 3%), lipase (2; 6%), all manageable. Median f/u was 19 mos: among 29 evaluable pts, median PFS was 12.9 mos, 95% CI = (7.4,-). Only 2 pts died. Peripherally, a significant increase in circulating T-regs (CD4+CD25hi+ Foxp3+; p=0.02 CD4+CD25hi+CD39+; p=0.001) from baseline to 6 wks was observed. Significant decreases in circulating MDSCs, were observed in monocytic HLA-DR+ / low/CD14+ MDSC (p&lt;0.0001). Greater increases in T-regs were associated with improved PFS (p=0.034; HR=0.57). Spontaneous in vivo cross-presentation was observed resulting in Th1CD4+ and CD8+ antigen specific T-cell immunity (gp-100, MART-1, NY-ESO-1 peptides). Significant fold increase (3-10-fold) in CD3+/CD4+/INF-γ+ antigen specific T cells was seen only in pts who were progression free at 6 mos. Baseline serum IL-17 correlates with grade 3 diarrhea (p=0.02). In tumor, Tregs appeared higher at wk 6 in PD group while the opposite in clinical benefit group (p=0.09). In tumor, Ipi induced TIL T-cell activation as evidenced by CD69 in the absence of other in vitro stimulation and induced T cell memory (CD45RO+) and not naïve (CD45RO-). By IHC, there was significant increase in CD8+ TIL after ipilimumab (p=0.02). Conclusions: Neoadjuvant ipi exhibited promising clinical activity and significantly modulated the host effector and suppressor immune response. Functional studies and prediction modeling analyses of biomarker findings are ongoing.
Toxicity and Effectivity of the Experimental Cytotoxic Drug Cyclopentenyl Cytosine in NOD/scid Mice with Acute Lymphoblastic Leukemia (ALL).
Authors: Kirsten J.M. Schimmel, Bart A. Nijmeijer, Marianke L.J. van Schie, J.H. Frederik Falkenburg, Henk-Jan Guchelaar
Journal: Blood (2005)
Thalidomide for the Treatment of Low Risk Myelodysplasia.
Authors: D. Bouscary, M. C. Quarre, D. Vassilief, O. Beyne Rouzy, A. Aouba, C. Berthou, C. Gardembas, L. Sanhes, A. Guerci, B. Mahe, A. Stamatoullas, F. Bauduer, J. J. Sotto, L. Legros, S. Vaultier, P. Fenaux, F. Dreyfus
Journal: Blood (2004)