tbuckley/cabot-search huggingface dataset:
P3-020: Combined CCL19/IL-7 treatment eradicates tumors in murine models of lung cancer
Authors: Stephan Arni, Markus Cardell, Seok-Chul Yang, Stephan Korom, Isabelle Opitz, Didier Lardinois, Sherven Sharma, Steven M. Dubinett, Walter Weder, Sven Hillinger
Journal: Journal of Thoracic Oncology (2007)
Genome-wide molecular characterization of mucinous colorectal adenocarcinoma.
Authors: H. Kim, S. Y. Rha, C. Park, H. C. Chung, H. Jeung, J. K. Roh, W. Yang, N. Kim
Journal: Journal of Clinical Oncology (2010)

e21042 Background: Mucinous colorectal carcinoma exhibits distinct clinicopathologic features compared to non-mucinous colorectal carcinoma. Previous studies have discovered several moleculargenetic features in mucinous colorectal carcinomas. Methods: To understand the systemic biology of mucinous colorectal carcinoma, this study was designed to identify differentially expressed genes (DEGs) in mucinous compared to nonmucinous colorectal carcinoma using cDNA 17k microarray chips in 25 mucinous and 27 non-mucinous cancer tissues. DEGs were determined by a Welch's t-test and more accurate classifiers were selected from DEGs via the Prediction Analysis for Microarray. Results: The identified gene set including upregulated TFF1 (4-fold), AGR2 (3.3- fold), FSCN1 (2.2-fold), CD44 (1.5-fold) and downregulated SLC26A3 (0.2-fold) in mucinous colorectal tissues was functionally investigated and genetic networks were generated. Sixty-two genes were determined and the 50 highest ranked genes of them could accurately classify mucinous and non- mucinous colorectal carcinomas. TFF1, AGR2, SLC26A3 were validated by quantitative real-time RT-PCR. The functions of these DEGs were related to tumorigenesis (14 genes), cell cycle progression (6 genes), invasion (2 genes), antiapoptosis (7 genes), cell adhesion and proliferation (5 genes) and carbohydrate metabolism (3 genes). The generated network also was associated with cancer invasion, mucin production and cell cycle progression. Conclusions: From the functional roles of these genes, we might suggest that expression signatures of the determined genes could contribute to invasiveness and poor prognosis of mucinous colorectal carcinoma and these gene set could provide better understanding of molecular pathogenesis. No significant financial relationships to disclose.
Could abatacept directly target expanded plasmablasts in IgG4-related disease?
Authors: Guillermo Carvajal Alegria, Pierre Pochard, Jacques-Olivier Pers, Divi Cornec
Journal: Annals of the Rheumatic Diseases (2016)

Yamamoto et al 1 recently reported the case of a patient with long-standing and relapsing IgG4-related disease (IgG4-RD), who developed secondary resistance to rituximab treatment but subsequently improved under abatacept infusions. This interesting observation drives important questions, regarding both IgG4-RD pathophysiology and abatacept mechanisms of action.

IgG4-RD is a systemic disease of unknown cause, affecting primarily middle-aged men, characterised by swelling of one or several organs (mainly pancreas, salivary and lachrymal glands, lymphadenopathy, retroperitoneal organs) with infiltration of IgG4-positive plasma cells and fibrosis of involved organs, and high serum IgG4 levels in half of the patients.2 ,3 Several diagnostic or classification systems have been proposed.4 ,5

Its pathophysiology is still ill-defined.6 IgG4-secreting plasmablasts are central players in the disease: they are the main infiltrating cells in affected organs, they are expanded in the circulation, are …
Feasibility study of cationic liposome-encapsulated paclitaxel in combination with paclitaxel followed by FEC as induction therapy in HER2-negative breast cancer.
Authors: Michail Ignatiadis, Marc Lemort, Celine Wilke, Marie-Catherine Vanderbeeken, Veronique D'hondt, Andrea Gombos, Evandro De Azambuja, Fabienne Lebrun, Lissandra Dal Lago, Marion Maetens, Lieveke Ameye, Isabelle Veys, Stefan Michiels, Marianne Paesmans, Denis Larsimont, Christos Sotiriou, Jean-Marie Nogaret, Martine J. Piccart-Gebhart, Ahmad Awada
Journal: Journal of Clinical Oncology (2013)

e12008 Background: Cationic liposome-encapsulated paclitaxel , a tumor endothelial targeting agent (composition of paclitaxel combined with neutral and cationic lipids) has shown activity in metastatic triple-negative breast cancer (BC) in combination with paclitaxel (Awada et al. ESMO2010). No data exist in the non-metastatic setting. Methods: HER2-negative BC candidates for neoadjuvant chemotherapy were scheduled to receive 12 cycles of weeklycationic liposome-encapsulated paclitaxel 22mg/m2 plus paclitaxel 70mg/m2 followed by 3 cycles of FEC (Fluorouracil 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2) every 3 weeks followed by surgery. Primary endpoint was percent (%) reduction in Magnetic Resonance Imaging (MRI) estimated tumor volume at the end of cationic liposome-encapsulated paclitaxel plus paclitaxel administration as compared to baseline. Safety, pathological complete response (pCR) defined as no residual tumor in breast and axillary nodes at surgery and correlation between % reduction in MRI estimated tumor volume and pCR were also evaluated. Results: Six patients with estrogen receptor (ER)-negative/HER2-negative and 9 with ER-positive/HER2-negative BC were included. Nine patients completed treatment as per protocol. Despite premedication and slow infusion rates, grade 3 hypersensitivity reactions to cationic liposome-encapsulated paclitaxel were observed during the 1 st , 2 nd , 3 rd and 6 th weekly infusion in 4 patients, respectively and required permanent discontinuation of the cationic liposome-encapsulated paclitaxel . Two patients stopped cationic liposome-encapsulated paclitaxel plus paclitaxel after 8 and 9 weeks due to clinical disease progression, two patients had grade 3 increase in transaminases and 1 patient grade 4 neutropenia. PCR was observed in 5 of the 6 ER-/HER2- and in none of the 8 ER+/HER2- BC patients. The median % reduction in MRI estimated tumor volume at the end of cationic liposome-encapsulated paclitaxel plus paclitaxel treatment was 90% (95% Confidence Interval: 69-99%), (p&lt;0.001, sign test) for the 14 patients that underwent surgery; 99% (CI:87-100%) for patients with pCR and 84% (CI:50-95%) for patients with no pCR. Conclusions: The cationic liposome-encapsulated paclitaxel and paclitaxel combination showed promising preliminary activity as preoperative treatment, especially in ER-/HER2- patients. Further studies are warranted with need of premedication optimization. Clinical trial information: NCT01537536.
Long-term Cost-effectiveness in the Veterans Affairs Open vs Endovascular Repair Study of Aortic Abdominal Aneurysm
Authors: Frank A. Lederle, Kevin T. Stroupe, Tassos C. Kyriakides, Ling Ge, Julie A. Freischlag
Journal: JAMA Surgery (2016)

<h3>Importance</h3> Because of the similarity in clinical outcomes after elective open and endovascular repair of abdominal aortic aneurysm (AAA), cost may be an important factor in choosing a procedure. <h3>Objective</h3> To compare total and AAA-related use of health care services, costs, and cost-effectiveness between groups randomized to open or endovascular repair. <h3>Design, Setting, and Participants</h3> This unblinded randomized clinical trial enrolled 881 patients undergoing planned elective repair of AAA who were candidates for open and endovascular repair procedures. Patients were randomized from October 15, 2002, to April 15, 2008, at 42 Veterans Affairs medical centers. Follow-up was completed on October 15, 2011, and data were analyzed from April 15, 2013, to April 15, 2016, based on intention to treat. <h3>Main Outcomes and Measures</h3> Mean total and AAA-related health care cost per life-year and per quality-adjusted life-year (QALY). <h3>Results</h3> A total of 881 patients (876 men [99.4%]; 5 women [0.6%]; mean [SD] age, 70 [7.8] years) were included in the analysis. After a mean of 5.2 years of follow-up, mean life-years were 4.89 in the endovascular group and 4.84 in the open repair group (<i>P</i> = .68), and mean QALYs were 3.72 in the endovascular group and 3.70 in the open repair group (<i>P</i> = .82). Total mean health care costs did not differ significantly between the 2 groups (endovascular group, $142 745; open repair group, $153 533; difference, −$10 788; 95% CI, −$29 796 to $5825;<i>P</i> = .25). Costs related to AAA, including the initial repair, constituted nearly 40% of total costs and did not differ significantly between the 2 groups (endovascular group, $57 501; open repair group, $57 893; difference, −$393; 95% CI, −$12 071 to $7928;<i>P</i> = .94). Lower costs due to shorter hospitalization for initial endovascular repair were offset by increased costs from AAA-related secondary procedures and imaging studies. The probability of endovascular repair being less costly and more effective was 56.8% when effectiveness was measured in life-years and 55.4% when effectiveness was measured in QALYs for total costs and 31.3% and 34.3%, respectively, for AAA-related costs. <h3>Conclusions and Relevance</h3> In this multicenter randomized clinical trial with follow-up to 9 years, survival, quality of life, costs, and cost-effectiveness did not differ between elective open and endovascular repair of AAA. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00094575
MicroRNA Expression Profiles in Acute Myeloid Leukemia with Common Translocations.
Authors: Zejuan Li, Jun Lu, Miao Sun, Shuangli Mi, Hao Zhang, Roger T. Luo, Zhijian Qian, Mary Beth Neilly, Yungui Wang, Jie Jin, Yanming Zhang, Stefan K. Bohlander, Richard Larson, Michelle LeBeau, Michael J. Thirman, Todd R. Golub, Janet D. Rowley, Jianjun Chen
Journal: Blood (2007)
Vinflunine maintenance therapy versus best supportive care (BSC) after platinum combination in advanced bladder cancer: A phase II, randomized, open-label study (MAJA study)—SOGUG 2011-02.
Authors: Sonia Maciá, Jesus Garcia-Donas, Albert Font Pous, Montserrat Domenech, Xavier Garcia del Muro, Begoña Mellado, Javier Puente, Jose Angel Arranz Arija, Miguel Angel Climent Duran, Nuria Lainez Milagro, Jose Luis Perez-Gracia, Aranzazu Gonzalez del Alba, José Carlos Villa Guzman, Begoña Pérez-Valderrama, Juan Virizuela Echaburu, Teresa Bonfill, Luis Leon Mateos, Rafael Morales-Barrera, Daniel E. Castellano, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2012)

TPS4674 Background: Vinflunine is a novel microtubule inhibitor currently approved by EMA as treatment after platinum progression, in metastasic bladder cancer. It is distinguished from the other vinca-alkaloids because it binds relatively weakly to tubulin, suggesting an improved tolerance profile as a result of less neuropathy. Based on the fact that no cumulative toxicity is expected and the results reported in second-line, we aim to test the role of vinflunine in first line therapy, as maintenance treatment for patients who obtain clinical benefit after platinum. Methods: This is a multicenter, randomized, open label, proof-of-concept study that will be performed in 20 institutions members of the Spanish Oncology Genitourinary Group (SOGUG). Subjects will be randomized in a 1:1 ratio to receive vinflunine 320 mg/m2 every 21 days plus BSC vs BSC alone until disease progression. Vinflunine dose will be 280mg/m2 for patients with PS=1, age ≥ 75 years, prior pelvic radiotherapy or creatinine clearance Cr &lt;60ml/min. Stratification factors are: 1) Scheduled dose at randomization (320 vs 280mg/m2) 2) Liver metastasis (Y/N). Main inclusion criteria are: Subjects ≥18 and&lt; 80 years of age with histological diagnosis of transitional cell carcinoma of the urothelial tract and measurable disease with radiological response or stabilization after 6 cycles of a platinum containing doublet for metastasic/advanced disease. Primary objective will be progression free survival (PFS), considering as clinically relevant 6 months in experimental arm. To guarantee an overall type-1 α error (one side) no greater than 0.05 and a type II (β) error 0.1 for the primary endpoint of PFS, a sample size of 86 patients allocated in a 1:1 ratio is planned. Recruitment is scheduled to start by February 2012. A pharmacogenomic translational study will also be conducted.
Abstract 1019: hnRNPA2/B1 upregulates COX-2 expression and tumor growth and predicts poor prognosis in human lung cancers
Authors: Jingshu Wang, Yang Xuan, Wei Guo, Guangwei Du, Wuguo Deng
Journal: Cancer Research (2015)

Abstract Constitutive high expression of COX-2 can promote tumor development and has been regarded as a hallmarker for cancers. However, the excise regulation mechanism of COX-2 and its role in lung tumoirgenesis remains unknown. In this study, we discovered and identified hnRNPA2/B1 as a novel regulator of COX-2 promoter in non-small cell lung cancer (NSCLC) cells by a DNA probe-biotin-streptavidin-agarose pulldown and proteomic technique. We showed that hnRNPA2/B1 specifically bound to COX-2 core promoter region, activated COX-2 promoter activity and up-regulated COX-2 expression. Knockdown of hnRNPA2/B1 expression by siRNA significantly suppressed tumor cell growth in NSCLC cell lines in vitro and in a animal model in vivo by inhibiting COX-2 expression. In contrast, overexpression of hnRNPA2/B1 promoted COX-2 expression and tumor cell growth in NSCLC cells. Micro-tissue array and immunohistochemical assay showed that hnRNPA2/B1 expression correlated with COX-2 expression and high expression of hnRNPA2/B1 and COX-2 was associated with worse prognosis in patients with NSCLCs. Mechanistically, hnRNPA2/B1 functions as a regulator of COX-2 to control tumor growth through its interaction with p300, a transcriptional co-activator, in NSCLC cells. Immunoprecipitation and confocal immunofluorescence microscope analysis confirmed the direct interaction of hnRNPA2/B1 with p300 proteins. Overexpression of p300, but not its histon acetyltransferase domain deletion mutation, enhanced the acetylation of hnRNPA2/B1, facilitated the binding of hnRNPA2/B1 to COX-2 promoter, thereby promoted COX-2 expression and tumor cell growth. Therefore, these results indicate that hnRNPA2/B1 acts as an activator to regulate COX-2 expression and tumor growth through the interaction with p300 in NSCLC cells and suggest that the hnRNPA2/B1/COX-2 signaling is a potential therapeutic target for lung cancers. Note: This abstract was not presented at the meeting. Citation Format: Jingshu Wang, Yang Xuan, Wei Guo, Guangwei Du, Wuguo Deng. hnRNPA2/B1 upregulates COX-2 expression and tumor growth and predicts poor prognosis in human lung cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1019. doi:10.1158/1538-7445.AM2015-1019
A phase Ib/II open-label study to evaluate the safety and efficacy of TRU-016 in combination with bendamustine versus bendamustine alone in patients with relapsed chronic lymphocytic leukemia.
Authors: F. T. Awan, J. M. Pagel, A. Goy, R. M. Rifkin, B. J. Poiesz, A. R. Mato, S. C. Stromatt, J. C. Byrd, U. Jaeger
Journal: Journal of Clinical Oncology (2011)

e13053 Background: CD37 is a member of the tetraspanin superfamily of molecules, which are implicated in diverse processes including cellular activation and proliferation, cell motility, and cell‐cell adhesion. CD37 is expressed constitutively at high levels on normal and transformed B-cells across a wide range of maturational stages. TRU-016 is a novel humanized anti-CD37 SMIP protein, which is a single chain Fv-Fc fusion protein. Pre-clinical studies have demonstrated that anti-CD37 SMIP protein mediates significantly greater direct and Fc mediated cellular killing of CLL cells than alemtuzumab or rituximab. A dose escalating phase I study in 57 patients with TRU-016 was recently completed. The highest dose tested was 20 mg/kg and a MTD was not reached. Methods: This international, multi-center, Phase Ib/II study is designed to determine a safe and tolerable dose of TRU-016 that can be used in combination with bendamustine in patients with relapsed CLL. In the initial dose-escalation phase Ib part of the study, 2 different doses of TRU-016 (15 mg/kg and 20 mg/kg) in combination with bendamustine will be studied in two cohorts of 6 patients each. The dosing of TRU-016 will be weekly for the first two 28-day cycles and then every 14 days for the next four 28-day cycles. Bendamustine (70 mg/m2) is administered after TRU-016 on days 1 and 2 of each 28-day cycle for 6-cycles. The MTD will be defined as the highest dose level of TRU-016 at which ≤1 of 6 patients in a cohort experience a DLT during Cycle 1 of treatment. This dose will subsequently be utilized in the phase II component of the study in which 100 patients will be randomized in a 1:1 ratio to one of two arms: TRU-016 plus bendamustine or bendamustine alone. Clinical activity endpoints will include tumor response, duration of response, time to tumor progression, and progression-free survival. OS and QOL data will also be collected. Results: The phase Ib trial is currently open to accrual and enrollment is estimated to require 6-9 months. Phase 2 enrollment is estimated to require 12–15 months. Conclusions: This trial is registered at www.ClinicalTrials.gov as NCT01188681.
P2-318: Activity of intravenous Topotecan in patients with advanced non-small cell lung cancer pre-treatred with platinum and taxanes: Results of the first analysis
Authors: Noemi Villanueva, Emilio Esteban, Beatriz Llorente, Yolanda Fernández, Paula Jimenez, Marta Capelan, Joaquin Fra, Jose María Vieitez, Isabel Muñiz, Angel J. Lacave
Journal: Journal of Thoracic Oncology (2007)
Is it possible to predict nonplatinum chemotherapy-related toxicity?
Authors: S. Lheureux, V. Launay-Vacher, K. Gunzer, C. Delcambre, K. Bouhier, L. Kaluzinski, M. Ngo, D. Maron, G. Zalcman, F. Joly
Journal: Journal of Clinical Oncology (2010)

e19688 Background: Adverse effects induced by cytotoxic chemotherapy (CT) have been mostly evaluated in clinical trials. Anticancer drug dosage is usually based on body surface area except for platinum-based CT. The study objective was to assess in nonselected pts the incidence of nonplatinum CT-related toxicity and to identify risk factors useful in daily practice. Methods: Pts treated with nonplatinum-based CT for a solid tumor were included in a prospective observational study. Age, sex, tumor location, CT, PS, blood cell count, renal function (Cockcroft-Gault formula, proteinuria) and albumin were assessed at baseline. Multivariate logistic regression was used to identify risk factors. Results: From October 2007 to December 2008, 502 pts were recruited in 6 hospitals in Normandy, France. Most common sites were breast (54%) and digestive (30%) cancers; 46% of pts were metastatic. Pts characteristics were: F/M ratio 2.3; mean age 58 yrs (22 to 85); PS ≥ 1 29%; creatinine clearance (Clcreat) < 90 mL/min 47%; albumin < 35 g/l 31%. On CT, 62% of pts had grade (G) 2-4 toxicity, G 3-4 neutropenia or G 3-4 nausea-vomiting, of whom 20% developed infection requiring antibiotics. Hematologic toxicities were 34% including G 3-4 neutropenia 13%; G 2-4 anemia 17%; G 2-4 thrombopenia 4%; and febrile neutropenia 8%. Other toxicities were digestive 16%; dermatologic 11%; and neurologic 11%. On average, toxicities occurred during the 3rd course of CT. In 55% of pts, toxicity resulted in dose reduction (59%), delayed (25%) or discontinuation (16%) of CT. In multivariate analysis, breast cancer (OR = 4.35, P = 0.002), PS ≥ 1 (OR = 2.01, p = 0.011), lymphopenia < 800/mm3 (OR = 2.27, p = 0.026), albumin < 35 g/l (OR = 1.63, p = 0.047) and Clcreat < 60 mL/min ( OR = 1.92, p = 0.043) were risk factors for hematologic toxicity independently of CT type (adjuvant or metastatic). Overall, PS ≥ 1 (OR = 2.98, p<0.0001), Clcreat < 90 mL/min (OR = 1.99, p = 0.005), proteinuria (OR = 2.22, p = 0.033) and albumin < 35g/L (OR = 1.90, p = 0.012) were risk factors for change of CT schedule. Conclusions: A majority of pts given nonplatinum CT experience early significant toxicity leading to change of standard CT protocol. Albumin, creatinine clearance and lymphocyte should be routinely monitored to manage CT. No significant financial relationships to disclose.
Persistence of interleukin (IL)-17A<sup>+</sup> T lymphocytes and IL-17A expression in treatment-resistant psoriatic plaques despite ustekinumab therapy
Authors: C. Jack, S. Mashiko, N. Arbour, R. Bissonnette, M. Sarfati
Journal: British Journal of Dermatology (2016)

With the widespread use of monoclonal antibodies directed against cytokines in the treatment of psoriasis, we are presented with opportunities to investigate paradigms in cutaneous immunology, notably with respect to the ongoing skin inflammation that ‘escapes’ these therapies.

Ustekinumab, a monoclonal antibody targeting the shared p40 subunit of IL-12 and IL-23, is a frequently used systemic treatment for psoriasis, blocking both Th1 and Th17 responses. Interestingly, most ‘responders’ to biologics, still have areas of persistent disease involvement, often presenting with moderate-to-severe psoriatic plaques, localized to one or a few locations on the body while under treatment.

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Surveillance des infections systémiques invasives à streptocoque du groupe A en Italie, 1994-1996
Authors: B Suligoi, C Von Hunolstein, G Orefici, F Scopetti, M Pataracchia, D Greco
Journal: Eurosurveillance (1998)

A la suite de rapports sur une epidemie d'infections a streptocoque beta-hemolytique du groupe A (SGA) au Royaume Uni (1), l'Istituto Superiore di Sanita (ISS) a etabli un systeme de surveillance pour les infections systemiques invasives a SGA a la fin du mois de mai 1994. Cette initiative repondait egalement a une demande de l'Organisation Mondiale de la Sante (OMS) en mai 1994 pour la mise en place de systemes de surveillance specifiques de ces infections a travers l'Europe (2). Les objectifs de ce systeme etaient de collecter les donnees sur la survenue de ces infections en Italie et d'identifier les episodes epidemiques.