tbuckley/cabot-search huggingface dataset:
Population Gene Introgression and High Genome Plasticity for the Zoonotic Pathogen Streptococcus agalactiae
Authors: Vincent P Richards, Irina M Velsko, Md Tauqeer Alam, Ruth N Zadoks, Shannon D Manning, Paulina D Pavinski Bitar, Hayley B Hassler, Chiara Crestani, Garrett H Springer, Brett M Probert, Christopher D Town, Michael J Stanhope
Journal: Molecular Biology and Evolution (2019)

The influence that bacterial adaptation (or niche partitioning) within species has on gene spillover and transmission among bacterial populations occupying different niches is not well understood. Streptococcus agalactiae is an important bacterial pathogen that has a taxonomically diverse host range making it an excellent model system to study these processes. Here, we analyze a global set of 901 genome sequences from nine diverse host species to advance our understanding of these processes. Bayesian clustering analysis delineated 12 major populations that closely aligned with niches. Comparative genomics revealed extensive gene gain/loss among populations and a large pan genome of 9,527 genes, which remained open and was strongly partitioned among niches. As a result, the biochemical characteristics of 11 populations were highly distinctive (significantly enriched). Positive selection was detected and biochemical characteristics of the dispensable genes under selection were enriched in ten populations. Despite the strong gene partitioning, phylogenomics detected gene spillover. In particular, tetracycline resistance (which likely evolved in the human-associated population) from humans to bovine, canines, seals, and fish, demonstrating how a gene selected in one host can ultimately be transmitted into another, and biased transmission from humans to bovines was confirmed with a Bayesian migration analysis. Our findings show high bacterial genome plasticity acting in balance with selection pressure from distinct functional requirements of niches that is associated with an extensive and highly partitioned dispensable genome, likely facilitating continued and expansive adaptation.
KRAS mutation, cancer recurrence, and patient survival in stage III colon cancer: Findings from CALGB 89803
Authors: C. Fuchs, S. Ogino, J. A. Meyerhardt, N. Irahara, D. Niedzwiecki, D. Hollis, L. B. Saltz, R. J. Mayer, M. M. Bertagnolli
Journal: Journal of Clinical Oncology (2009)

4037 Purpose: KRAS mutation in stage IV colorectal cancer predicts resistance to anti-EGFR targeted treatment (cetuximab or panitumumab). However, whether the presence of KRAS mutation independently predicts the survival of colon cancer patients remains uncertain. Methods: We conducted a prospective observational study of 508 cases identified among 1264 patients with stage III colon cancer who enrolled in a randomized adjuvant chemotherapy trial (5-fluorouracil, leucovorin with or without irinotecan) between April 1999 and May 2001 (CALGB 89803; Saltz et al. J Clin Oncol 2007). KRAS mutations were detected in 178 tumors (35%) by Pyrosequencing. Kaplan-Meier and Cox proportional hazard models were used to assess the significance of KRAS mutational status and adjusted for potential confounders including age, sex, tumor location, T stage, N stage, performance status, adjuvant chemotherapy arm and microsatellite instability (MSI) status. Results: When compared to patients with wild-type KRAS, those with a mutation in KRAS did not experience any difference in disease-free (DFS), recurrence-free (RFS), or overall survival (OS) (log-rank P&gt;0.56 for DFS, RFS, and OS). Five-year DFS was 62% for KRAS-mutated and 63% for KRAS-wild-type patients. Five-year RFS was 64% for KRAS-mutated and 66% for KRAS- wild-type patients. Five-year OS was 74% for KRAS-mutated and 73% for KRAS-wild-type patients. The effect of KRAS mutation on patient survival did not differ according to clinical features, chemotherapy arm or MSI status, and the effect of adjuvant chemotherapy assignment on outcome did not differ according to KRAS status. Conclusions: In this large clinical trial of chemotherapy in patients with stage III colon cancer, KRAS mutational status was not associated with any significant influence on disease-free or overall survival. No significant financial relationships to disclose.
Fexofenadine inhibits TNF signaling through targeting to cytosolic phospholipase A2 and is therapeutic against inflammatory arthritis
Authors: Ronghan Liu, Yuehong Chen, Wenyu Fu, Shuya Wang, Yazhou Cui, Xiangli Zhao, Zi-Ning Lei, Aubryanna Hettinghouse, Jody Liu, Chao Wang, Chen Zhang, Yufei Bi, Guozhi Xiao, Zhe-Sheng Chen, Chuan-ju Liu
Journal: Annals of the Rheumatic Diseases (2019)

Objective Tumour necrosis factor alpha (TNF-α) signalling plays a central role in the pathogenesis of various autoimmune diseases, particularly inflammatory arthritis. This study aimed to repurpose clinically approved drugs as potential inhibitors of TNF-α signalling in treatment of inflammatory arthritis. Methods In vitro and in vivo screening of an Food and Drug Administration (FDA)-approved drug library; in vitro and in vivo assays for examining the blockade of TNF actions by fexofenadine: assays for defining the anti-inflammatory activity of fexofenadine using TNF-α transgenic (TNF-tg) mice and collagen-induced arthritis in DBA/1 mice. Identification and characterisation of the binding of fexofenadine to cytosolic phospholipase A2 (cPLA2) using drug affinity responsive target stability assay, proteomics, cellular thermal shift assay, information field dynamics and molecular dynamics; various assays for examining fexofenadine inhibition of cPLA2 as well as the dependence of fexofenadine’s anti-TNF activity on cPLA2. Results Serial screenings of a library composed of FDA-approved drugs led to the identification of fexofenadine as an inhibitor of TNF-α signalling. Fexofenadine potently inhibited TNF/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) signalling in vitro and in vivo, and ameliorated disease symptoms in inflammatory arthritis models. cPLA2 was isolated as a novel target of fexofenadine. Fexofenadine blocked TNF-stimulated cPLA2 activity and arachidonic acid production through binding to catalytic domain 2 of cPLA2 and inhibition of its phosphorylation on Ser-505. Further, deletion of cPLA2 abolished fexofenadine’s anti-TNF activity. Conclusion Collectively, these findings not only provide new insights into the understanding of fexofenadine action and underlying mechanisms but also provide new therapeutic interventions for various TNF-α and cPLA2-associated pathologies and conditions, particularly inflammatory rheumatic diseases.
A phase II study with gemcitabine and split-dose cisplatin in patients with advanced non-small cell lung cancer
Authors: H. Jang, J. Park, J. Kwon, J. Jung, H. Kim, H. Song, D. Zang, J. Lee, Y. Park, J. Kim
Journal: Journal of Clinical Oncology (2006)

17115 Background: The combination of gemcitabine and cisplatin is among the most active regimens for the treatment of NSCLC. However, the optimal dose and schedule for administration of the two drugs has not yet been determined. We investigated the activity and toxicity of a gemcitabine and split-dose cisplatin regimen in an outpatient setting for patients with advanced non-small cell lung cancer (NSCLC). Methods: From June 2004 to May 2005 patients with stage IIIB or IV who had not had prior chemotherapy entered the study. Treatment consisted of gemcitabine 1,250 mg/m 2 and cisplatin 35 mg/m 2 , both given intravenously on days 1 and 8 every 21 days. Results: Forty-three patients were entered this study. Patient characteristics were as follows: male/female, 32/11; median age (range), 63 (30–76) years; ECOG PS 0/1/2, 7/28/8; stage IIIB/IV, 17/26. A total of 160 cycles were delivered, with a median of 4 cycles (range, 1–6). All patients were evaluable for toxicity. Grade 3 &amp; 4 toxicities according the NCI toxicity criteria included included neutropenia in 7 patients (17%), anemia in 3 (7%), thrombocytopenia in 6 (14%), and emesis in 1 (2%). Of 40 patients assessable for response, one (2.5%) had CR and 22 (55%) had PR. On intent-to-treat basis, the overall response rate was 53% (95% CI, 39–68%). Median time to progression was 6.0 months (range, 1.2–12.0 months) and median overall survival was 13.1 months (range, 1.4–17 months). Conclusions: This regimen with gemcitabine and split-dose cisplatin using a 21-day schedule appears to be active and very well-tolerated in an outpatients setting for patients with advanced NSCLC. No significant financial relationships to disclose.
Recombinant growth/differentiation factor-5 enhances cell proliferation and tendogenic differentiation of human periodontal ligament stem cells in vitro.
Authors: Dengsheng Xia, Yoshinori Sumita, Simon Tran
Journal: Journal of Clinical Oncology (2013)

e22191 Background: To investigate the function of growth/differentiation factor-5 (GDF-5) on cell proliferation and tendogenic differentiation of human periodontal ligment stem cells (PDLSCs) in vitro. Methods: PDLSCs were obtained from human healthy periodontal ligaments of wisdom teeth. Immunofluorescence cytochemistry was used to detect the characters of mesenchymal stem cells (MSCs) in PDLSCs. Recombinant mouse GDF-5 (rmGDF-5) protein was used to stimulate the PDLSCs. Tetrazolium reduction assay was carried out for cell proliferation. Alkaline phosphatase (ALP) activity was measured by ALP activity assay and ALP staining. Real-time RT-PCR was performed to detect the gene expressions of aggrecan (ACAN), collagen, type III (COL3), scleraxis (SCX), decorin (DCN), tenomodulin (TNMD) and tenascin C (TNC) in PDLSCs after stimulated by rmGDF-5 protein. Results: 5.6% STRO-1 positive cells was detected in primary PDLSCs. The cell proliferation of PDLSCs was enhanced by rmGDF-5 in a dose-dependent manner at 0, 20, 100 and 500 ng/ml of concentration. The special markers of tendogenic differention, ACAN, COL3, SCX and TNMD were up-regulated at mRNA level after rmGDF-5 treatment for 1, 2 or 3 weeks, and the 20 ng/ml was the more effective than 100 ng/ml and 500 ng/ml for rmGDF-5 in PDLSCs. The expressions of TNC and DCN were increased at 4 or 8 hours after 20, 50 and 100 ng/m rmGDF-5 treatment. The ALP activity results showed that ALP activities were decreased paralleled with increased rmGDF-5 concentration. Conclusions: The rmGDF-5 could promote the cell proliferation and tendogenic differentiation of PDLSCs in vitro.
Comparison of apixaban to rivaroxaban and enoxaparin in acute cancer‐associated venous thromboembolism
Authors: Waldemar E. Wysokinski, Damon E. Houghton, Ana I. Casanegra, Danielle T. Vlazny, Dalene M. Bott‐Kitslaar, David A. Froehling, David O. Hodge, Lisa G. Peterson, Robert D. Mcbane
Journal: American Journal of Hematology (2019)

To provide direct comparison between apixaban and rivaroxaban in patients with acute cancer-associated venous thromboembolism (Ca-VTE), consecutive patients treated with apixaban, rivaroxaban, or enoxaparin at Mayo Thrombophilia Clinic (March 1, 2013 to January 31, 2018)) were followed prospectively. The primary effectiveness outcome was venous thromboembolism (VTE) recurrence, and the secondary was mortality. The primary safety outcome was major bleeding, the secondary clinically relevant safety outcome was non-major bleeding (CRNMB), and the third a composite of major and CRNMB. There were 750 patients treated for acute Ca-VTE with apixaban (n = 224), rivaroxaban (n = 163), and enoxaparin (n = 363) within 14 days of diagnosis and for at least 3 months, or until study event. Recurrent VTE was diagnosed in 11 receiving apixaban, 7 receiving rivaroxaban (apixaban vs rivaroxaban hazard ratio (HR) 1.31, 95% confidence interval (95% CI) 0.51-3.36) and 17 in the enoxaparin receiving group (apixaban vs enoxaparin HR 1.14, 95% CI: 0.54, 2.42 and rivaroxaban vs enoxaparin HR 0.85, 95% Cl: 0.36, 2.06). There were 82 deaths in apixaban, 74 rivaroxaban (apixaban vs rivaroxaban HR 1.67, 95% Cl: 1.20, 2.33) and 171 in enoxaparin group (rivaroxaban vs enoxaparin HR 0.73, 95% Cl: 0.56, 0.96). Major bleeding occurred in 11 apixaban, 12 rivaroxaban (apixaban vs rivaroxaban HR 0.73, 95% Cl: 0.32, 1.66) and 21 enoxaparin group (apixaban vs enoxaparin HR 0.89, 95% Cl: 0.43, 1.84 and rivaroxaban vs enoxaparin HR 1.23, 95% Cl: 0.61, 2.50). The CRNMB rate was higher in rivaroxaban compared to apixaban (P = .03) and LMWH (P = .01) groups. Recurrence of VTE and major bleeding were similar in apixaban, rivaroxaban, and enoxaparin groups. Rivaroxaban was associated with higher CRNMB but lower mortality compared to apixaban and enoxaparin.
Connecting Students with Patients and Survivors to Enhance Cancer Research Training
Authors: Robert N. Riter, Robert S. Weiss
Journal: Cancer Research (2019)

Abstract The professional training of cancer researchers in the basic sciences rarely involves interactions with patients. To provide nascent cancer scientists with an appreciation for and experience in interacting with the people most vested in their work, we created a program at Cornell University in which cancer researchers in training engage with the local patient community. Through this program, trainees gain a broader understanding of cancer, beyond the fundamental biology, and learn to effectively communicate scientific information to the public. We find that trainees and community members both benefit from interacting with one another and learning together about cancer using a common language.
Swallowing function after intensity modulated radiotherapy (IMRT) and chemotherapy for head and neck cancer
Authors: H. B. Caglar, A. M. Allen, E. Burke, M. Posner, R. Haddad, C. Norris, D. Annino, L. Wirth, R. Tishler
Journal: Journal of Clinical Oncology (2007)

6046 Background: To evaluate the swallowing function of patients treated with intensity modulated radiation therapy (IMRT) + chemotherapy (CT) for HNSCC. Methods: Patients completing RT between 9/04 and 8/06 at the DFCI/BWH were evaluated with IRB approval. All patients had formal swallowing evaluation following the completion of therapy; patients with swallowing difficulty underwent video swallow and both stricture and aspiration were scored. Variables examined for correlation with swallowing pathology were: age, race, gender, smoking and alcohol history, primary site, LVI, PNI, RT intention (primary, postop) and use of induction CT. All variables were analyzed via two-sided t-test. Results: 96 patients were evaluated. Median follow-up 10 mos. 75% of the pts were given definitive RT and 25% received postop RT. 72% stage IV, 24% stage III. Primary sites: oropharynx-43, hypopharynx/larynx-17, oral cavity-13, nasopharynx-11, maxillary sinus-2 and unknown primary-10 pts. All pts received once daily IMRT. 9 pts received RT alone, 28 pts received sequential induction and concurrent (CT) and 59 pts received concurrent CT. 31 pts (32%) had some aspiration after therapy; 36 pts (37%) had evidence of a stricture following RT. All but 5 patients had percutaneous endoscopic gastrostomy placed prophylactically RT. Smoking history was the only significant factor found on univariate analysis to correlate with stricture (p=0.05) but not aspiration. Induction CT was not a significant factor in causing aspiration or stricture. 22 of the strictures (71%) resolved after dilation. RT doses to swallowing structures are under evaluation and will be presented. Conclusions: Aspiration and stricture are common side effects after radical treatment with IMRT and CT for HNSCC. Smoking has a significant negative impact on functional outcome. No significant financial relationships to disclose.
Phase II trial to evaluate combination of folfox6 + bevacizumab in initially unresectable liver metastases from colorectal cancer (crc)
Authors: N. Malavasi, C. Dealis, R. Depenni, S. Zironi, F. Bertolini, L. Losi, G. E. Gerunda, G. Colucci, G. Luppi, P. F. Conte
Journal: Journal of Clinical Oncology (2007)

14603 Introduction: The gold standard treatment of CRC liver metastases is surgical resection. Bevacizumab has proved efficacy in advanced disease. Primary objective of the study is to evaluate resecability rate of liver metastases and incidence of major surgery complications. Secondary objective is to relate tumor and serum biomarkers (EGFR, VEGF, TS, Ki67, ERCC1, MSH2, MLH1 and VEGF ) to clinical outcome Methods: Baseline requires evaluation by CT-PET scan, biopsy of metastases; PET scan is needed after first administration to describe preliminary response. The treatment consists of FOLFOX6 regimen associated to Bevacizumab, 5mg/Kg, every two weeks; elective surgery is planned after 6 cycles (the last one excludes Bevacizumab dose) by CT-PET scan; if resection is appropriate, it will be performed, otherwise the treatment will continue to 12 cycles. Biomarkers are assessed at baseline, following the first administration and before surgery Results: Up to now 11 patients have been enrolled (M/F:6/5; median age:64, range:46–72); ECOG: 0/1. 10 patients reached surgical step while 1 patient is still on chemotherapy. Three patients (27%) were not suitable for resection and received further chemotherapy: 1 had PR, 1 PD and 1 became resectable after 12 cycles. In the other 7 patients (63%): 2 CR (18%) histologically confirmed; 4 macroscopic and curative resection of liver metastasis; 1 is receving two stage epathectomy (portal vein occlusion before major liver resection). Life threatening toxicities: 1 TVP causing discontinuation of Bevacizumab, 1 hospitalization for gastro-intestinal and G4 neutropenia both causing discontinuation of the whole therapy. Bevacizumab complications before major surgery did not occurred; 1 patient reported post operative delay wound healing. Less severe toxicities: haematological G3 in 2 patients (18%), G1 in 1 patient (9%); 3 gastrointestinal G2 (27%); neuropathic in 1 patient (9%). The VEGF serum decreased after the first dose of Bevacizumab in all specimens Conclusions: Systemic chemotherapy with combination regimens may downstage liver metastases and thus increase resecability rate without important surgery complications; biomarkers related to clinical outcome are in evaluation. No significant financial relationships to disclose.
Prevalence of acquired resistance mutations in a large cohort of perinatally infected HIV-1 patients
Authors: R. Ungaro, L. Taramasso, B. Bruzzone, I. Vicenti, L. Galli, V. Borghi, D. Francisci, M. Pecorari, A. Zoncada, A.P. Callegaro, E. Paolini, L. Monno, S. Bonora, A. Di Biagio, Andrea Giacometti, Luca Butini, Romana del Gobbo, Patrizia Bagnarelli, Danilo Tacconi, Giovanni Corbelli, Stefania Zanussi, Laura Monno, Grazia Punzi, Franco Maggiolo, Leonardo Calza, Maria Carla Re, Raffaele Pristera, Paola Turconi, Antonella Mandas, Sauro Tini, Alessia Zoncada, Elisabetta Paolini, Giorgio Amadio, Laura Sighinolfi, Paola Corsi, Luisa Galli, Massimo Di Pietro, Grazia Colao, Andrea Tosti, Maurizio Setti, Bianca Bruzzone, Antonio Di Biagio, Giovanni Cenderello, Michele Trezzi, Anna Orani, Irene Arcidiacono, Alberto Degiuli, Michele De Gennaro, Alessandro Chiodera, Alfredo Scalzini, Loredana Palvarini, Giovanni Todaro, Stefano Rusconi, Maria Rita Gismondo, Valeria Micheli, Maria Luisa Biondi, Amedeo Capetti, Paola Meraviglia, Enzo Boeri, Cristina Mussini, Monica Pecorari, Alessandro Soria, Laura Vecchi, Maurizio Santirocchi, Diego Brustia, Paolo Ravanini, Federico Dal Bello, Nino Romano, Salvatrice Mancuso, Carlo Calzetti, Renato Maserati, Gaetano Filice, Fausto Baldanti, Daniela Francisci, Giustino Parruti, Ennio Polilli, Daria Sacchini, Chiara Martinelli, Rita Consolini, Linda Vatteroni, Angela Vivarelli, Alessandro Nerli, Lucia Lenzi, Giacomo Magnani, Patrizia Ortolani, Massimo Andreoni, Caterina Fimiani, Lucia Palmisano, Simona Di Giambenedetto, Vincenzo Vullo, Ombretta Turriziani, Marco Montano, Andrea Antinori, Mauro Zaccarelli, Chiara Dentone, Angela Gonnelli, Andrea De Luca, Michele Palumbo, Valeria Ghisetti, Stefano Bonora, Palma Delle Foglie, Cristina Rossi, Vincenzo Mondino, Marina Malena, Paolo Grossi, Elena Seminari, Federica Poletti
Journal: Clinical Microbiology and Infection (2019)
The predictive accuracy of survival between patient-reported versus clinician-reported pain in a cohort of 1,214 patients with metastatic cancer
Authors: C. Quinten, F. Martinelli, C. Coens, C. S. Cleeland, H. Flechtner, C. Gotay, E. Greimel, M. J. Taphoorn, J. Weis, A. Bottomley
Journal: Journal of Clinical Oncology (2009)

9607 Background: Accurate assessment of pain involves cooperation between clinician and patient. However, in patients with metastatic disease agreement between clinician and patient ratings is known to be poor. The objectives of this meta-analysis are to investigate the degree of agreement between clinician- versus patient- reported cancer pain at entry in a cohort of patients with metastatic cancer and whether their ratings were associated with a difference in survival. Methods: Eight European Organisation for Research and Treatment of Cancer (EORTC) Randomized Controlled Trials (RCT), across different cancer sites, were eligible for this study. Pain was scored at baseline by the clinician [Common Toxicity Criteria (CTC)] and the patient (EORTC QLQ-C30). The Wilcoxon rank sign test was applied to investigate scoring differences between patient- versus clinician- reported pain and logistic regression to model whether clinical parameters, i.e., performance status, gender, age or cancer site, affected scoring differences. The model accuracy of both scorings was investigated with the Harrell's discrimination c-index (c) after correction for the clinical parameters. Results: 1214 patients provided valid patient- and clinician- reported pain data at entry. Cancer pain was specified as bone metastasis by 643 (53%) patients and not specified otherwise. The overall mean pain as scored by the clinician was 2.25 (standard deviation (SD) 1.1) and by the patient was 2.28 (SD=0.95) on a 1 to 4 scale. Scoring differences were found to be statistically significant for colorectal (p&lt;.01), lung (p&lt;.01), prostate (p&lt;.01), and breast (p=0.03, but not for pancreatic cancer (p=0.49). Clinical parameters did not significantly affect the scoring differences. Pain as reported by patients (vs clinicians) showed similar predictive accuracy (c =0.62 vs 0.61, p=0.59). Conclusions: Our results provide further evidence that significant differences exist in pain reporting between clinicians and patients. Such results provide a rationale to include patient self reported pain assessment in future cancer RCTs to better assess disease status and survival prognosis. No significant financial relationships to disclose.