tbuckley/cabot-search huggingface dataset:
Abstract 1251: Expression of NADPH oxidase 5 (Nox5) modulates cellular morphology, proliferation and invasiveness of human melanoma UACC-257 cells
Authors: Smitha Antony, Yongzhong Wu, Guojian Jiang, Jennifer L. Meitzler, Han Liu, Agnes Juhasz, Jiamo Lu, Miriam R. Anver, Krishnendu K. Roy, James H. Doroshow
Journal: Cancer Research (2015)

Abstract NADPH oxidase 5 (Nox5), one of the seven members of the NADPH oxidase gene family that generate reactive oxygen species (ROS), has been implicated in physiological and pathophysiological processes. Recently, we have reported substantial overexpression of Nox5 in several human cancers including those of prostate, ovary and melanomas; expression in most non-malignant tissues was weak to modest. Despite being upregulated in many human cancers and implicated in promoting cell proliferation, the molecular mechanisms regulated by Nox5 are poorly understood. In this study, the functional significance of Nox5 was assessed in human UACC-257 melanoma cells by generating stable Nox5-overexpressing clones and knockdown clones. Overexpression of Nox5 in UACC-257 cells resulted in enhanced cell growth, increased BrdU positive cells and decreased phosphatase activity. Additionally, these cells had increased normoxic Hif-1α expression and decreased p27Kip1 expression. Conversely, knockdown of endogenous Nox5 in UACC-257 cells resulted in decreased cell growth, decreased BrdU positive cells, decreased Hif-1α expression and increased p27Kip1 expression. Cadherin switch, loss of E-cadherin expression and upregulation of N-cadherin was observed in Nox5 overexpressing cells indicative of an invasive phenotype; conversely, an upregulation of E-cadherin expression in Nox5 knockdown cells was noted. Cell invasion assay through matrigel-coated membranes also demonstrated enhanced invasion by Nox5 overexpressing cells. Additionally, 3D cultures of Nox5 overexpressing cells exhibit an amoeboid morphology compared to that of the Nox5 knockdown cells that were mesenchymal, suggestive of an amoeboid - mesenchymal (AMT) transition. Strikingly, cells that overexpress Nox5 were able to proliferate in serum-free conditions for over a month. In summary, our findings suggest that Nox5 expression in human melanoma UACC-257 cells could contribute to cell proliferation, invasion, amoeboid morphology, and the ability to grow in the absence of serum or growth factors in part due to the generation of high local concentrations of extracellular ROS that modulate multiple signaling networks that regulate Hif-1α, p27Kip1, and the cadherin switch. Citation Format: Smitha Antony, Yongzhong Wu, Guojian Jiang, Jennifer L. Meitzler, Han Liu, Agnes Juhasz, Jiamo Lu, Miriam R. Anver, Krishnendu K. Roy, James H. Doroshow. Expression of NADPH oxidase 5 (Nox5) modulates cellular morphology, proliferation and invasiveness of human melanoma UACC-257 cells. [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 1251. doi:10.1158/1538-7445.AM2015-1251
Reoperation Rates in Ductal Carcinoma In Situ vs Invasive Breast Cancer After Wire-Guided Breast-Conserving Surgery
Authors: Linnea Langhans, Maj-Britt Jensen, Maj-Lis M. Talman, Ilse Vejborg, Niels Kroman, Tove F. Tvedskov
Journal: JAMA Surgery (2016)

<h3>Importance</h3> New techniques for preoperative localization of nonpalpable breast lesions may decrease the reoperation rate in breast-conserving surgery (BCS) compared with rates after surgery with the standard wire-guided localization. However, a valid reoperation rate for this procedure needs to be established for comparison, as previous studies on this procedure include a variety of malignant and benign breast lesions. <h3>Objectives</h3> To determine the reoperation rate after wire-guided BCS in patients with histologically verified nonpalpable invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) and to examine whether the risk of reoperation is associated with DCIS or histologic type of the IBC. <h3>Design, Setting, and Participants</h3> This nationwide study including women with histologically verified IBC or DCIS having wire-guided BCS performed between January 1, 2010, and December 31, 2013, used data from the Danish National Patient Registry that were cross-checked with the Danish Breast Cancer Group database and the Danish Pathology Register. <h3>Main Outcomes and Measures</h3> Reoperation rate after wire-guided BCS in patients with IBC or DCIS. <h3>Results</h3> Wire-guided BCS was performed in 4118 women (mean [SD] age, 60.9 [8.7] years). A total of 725 patients (17.6%) underwent a reoperation: 593 were reexcisions (14.4%) and 132 were mastectomies (3.2%). Significantly more patients with DCIS (271 of 727 [37.3%]) than with IBC (454 of 3391 [13.4%]) underwent a reoperation (adjusted odds ratio, 3.82; 95% CI, 3.19-4.58;<i>P</i> &lt; .001). After the first reexcision, positive margins were still present in 97 patients (16.4%). The risk of repeated positive margins was significantly higher in patients with DCIS vs those with IBC (unadjusted odds ratio, 2.21; 95% CI, 1.42-3.43;<i>P</i> &lt; .001). The risk of reoperation was significantly increased in patients with lobular carcinoma vs those with ductal carcinoma (adjusted odds ratio, 1.44; 95% CI 1.06-1.95;<i>P</i> = .02). A total of 202 patients (4.9%) had a subsequent completion mastectomy, but no difference was found in the type of reoperation between patients with DCIS and those with IBC. <h3>Conclusions and Relevance</h3> A lower reoperation rate after wire-guided BCS was found in this study than those shown in previous studies. However, the risk of reoperation in patients with DCIS was 3 times higher than in those with IBC. The widespread use of mammographic screening will increase the number of patients diagnosed with DCIS, making a precise localization of nonpalpable DCIS lesions even more important.
Association of Perioperative Statin Use With Mortality and Morbidity After Major Noncardiac Surgery
Authors: Martin J. London, Gregory G. Schwartz, Kwan Hur, William G. Henderson
Journal: JAMA Internal Medicine (2016)

The efficacy of statins in reducing perioperative cardiovascular and other organ system complications in patients undergoing noncardiac surgery remains controversial. Owing to a paucity of randomized clinical trials, analyses of large databases may facilitate informed hypothesis generation and more efficient trial design.To evaluate associations of early perioperative statin use with outcomes in a national cohort of veterans undergoing noncardiac surgery.This retrospective, observational cohort analysis included 180 478 veterans undergoing elective or emergent noncardiac surgery (including vascular, general, neurosurgery, orthopedic, thoracic, urologic, and otolaryngologic) who were admitted within 7 days of surgery and sampled by the Veterans Affairs Surgical Quality Improvement Program (VASQIP). Patients were admitted to Department of Veterans Affairs hospitals and underwent 30-day postoperative follow-up. Data were collected from October 1, 2005, to September 30, 2010, and analyzed from November 28, 2013, to October 31, 2016.Statin use on the day of or the day after surgery.All-cause 30-day mortality (primary outcome) and standardized 30-day cardiovascular and noncardiovascular outcomes captured by VASQIP. Use of statins and other perioperative cardiovascular medications was ascertained from the Veterans Affairs Pharmacy Benefits Management research database.A total of 180 478 eligible patients (95.6% men and 4.4% women; mean [SD] age, 63.8 [11.6] years) underwent analysis, and 96 486 were included in the propensity score-matched cohort (96.3% men; 3.7% women; mean [SD] age, 65.9 [10.6] years). At the time of hospital admission, 37.8% of patients had an active outpatient prescription for a statin, of whom 80.8% were prescribed simvastatin and 59.5% used moderate-intensity dosing. Exposure to a statin on the day of or the day after surgery based on an inpatient prescription was noted in 31.5% of the cohort. Among 48 243 propensity score-matched pairs of early perioperative statin-exposed and nonexposed patients, 30-day all-cause mortality was significantly reduced in exposed patients (relative risk, 0.82; 95% CI, 0.75-0.89; P < .001; number needed to treat, 244; 95% CI, 170-432). Of the secondary outcomes, a significant association with reduced risk of any complication was noted (relative risk, 0.82; 95% CI, 0.79-0.86; P < .001; number needed to treat, 67; 95% CI, 55-87); all were significant except for the central nervous system and thrombosis categories, with the greatest risk reduction (relative risk, 0.73; 95% CI, 0.64-0.83) for cardiac complications.Early perioperative exposure to a statin was associated with a significant reduction in all-cause perioperative mortality and several cardiovascular and noncardiovascular complications. However, the potential for selection biases in these results must be considered.
Comparison of platinum rechallenge and docetaxel in non-small cell lung cancer previously treated with chemoradiotherapy
Authors: Hisao Imai, Kyoichi Kaira, Akira Ono, Hiroaki Akamatsu, Tetsuhiko Taira, Reiko Yoshino, Hirotsugu Kenmotsu, Tateaki Naito, Haruyasu Murakami, Toshiaki Takahashi
Journal: Annals of Oncology (2015)
Accrual of Older Patients With Breast Cancer to Alliance Systemic Therapy Trials Over Time: Protocol A151527
Authors: Rachel A. Freedman, Jared C. Foster, Drew K. Seisler, Jacqueline M. Lafky, Hyman B. Muss, Harvey J. Cohen, Jeanne Mandelblatt, Eric P. Winer, Clifford A. Hudis, Ann H. Partridge, Lisa A. Carey, Constance Cirrincione, Alvaro Moreno-Aspitia, Gretchen Kimmick, Aminah Jatoi, Arti Hurria
Journal: Journal of Clinical Oncology (2017)

Purpose Despite increasing awareness of accrual challenges, it is unknown if accrual of older patients to breast cancer treatment trials is improving. Methods We examined accrual of older patients to Alliance for Clinical Trials in Oncology systemic therapy breast cancer trials during 1985-2012 and compared disease characteristics and reasons for therapy cessation for older (age ≥ 65 years and ≥ 70 years) versus younger (age &lt; 65 years and &lt; 70 years) participants. To examine accrual trends, we modeled age as a function of time, using logistic regression. Results Overall, 17% of study participants were ≥ 65 years of age. Approximately 15%, 24%, and 24% of participants in adjuvant, neoadjuvant, and metastatic trials were age ≥ 65 years, and 7%, 15%, and 13% were age ≥ 70 years, respectively. The odds of a patient age ≥ 65 years enrolling significantly increased over time for adjuvant trials (odds ratio [OR] per year, 1.04; 95% CI, 1.04 to 1.05) but decreased significantly for neoadjuvant and metastatic trials (OR, 0.62; 95% CI, 0.58 to 0.67 and OR, 0.98, 95% CI, 0.97 to 1.00). Similar trends were seen for those age ≥ 70 years but these were statistically significant for adjuvant and neoadjuvant trials only (OR, 1.05, 95% CI, 1.04 to 1.07; and OR, 0.57, 95% CI, 0.52 to 0.62). In general, those age ≥ 65 years ( v those &lt; 65 years) in adjuvant studies had a higher mean number of lymph nodes involved and more hormone receptor-negative tumors, although tumor sizes were similar. Early protocol treatment cessation was also more frequent in those age ≥ 65 years (50%) versus &lt; 65 years (35.9%) across trials. Conclusion Older patients with breast cancer remain largely underrepresented in cooperative group therapeutic trials. We observed some improvement in accrual to adjuvant trials but worsening of accrual for neoadjuvant/metastatic trials. Novel strategies to increase accrual of older patients are critical to meaningfully change the evidence base for this growing patient population.
Role of innate and adaptive immunity in obesity-associated metabolic disease
Authors: Tracey McLaughlin, Shelley E. Ackerman, Lei Shen, Edgar Engleman
Journal: Journal of Clinical Investigation (2017)

Chronic inflammation in adipose tissue, possibly related to adipose cell hypertrophy, hypoxia, and/or intestinal leakage of bacteria and their metabolic products, likely plays a critical role in the development of obesity-associated insulin resistance (IR). Cells of both the innate and adaptive immune system residing in adipose tissues, as well as in the intestine, participate in this process. Thus, M1 macrophages, IFN-γ-secreting Th1 cells, CD8+ T cells, and B cells promote IR, in part through secretion of proinflammatory cytokines. Conversely, eosinophils, Th2 T cells, type 2 innate lymphoid cells, and possibly Foxp3+ Tregs protect against IR through local control of inflammation.
Abstract 5519: Engineered protein nanocage for targeted delivery of siRNA to cancer cells
Authors: Eun Jung Lee, Yoosoo Yang, In-san Kim, Kwangmeyung Kim, Jeewon Lee
Journal: Cancer Research (2015)

Abstract Considering the problems of small interfering RNA (siRNA) delivery using traditional viral and non-viral vehicles, a new siRNA delivery system to enhance efficiency and safety needs to be developed. Here we genetically engineered human ferritin based protein nanocage to simultaneously display various functional peptides on the surface of protein nanocage: cationic peptide to capture siRNA, tumor cell targeting and penetrating peptides, and enzymatically cleaved peptide to release siRNA inside tumor cell. In particular, we easily changed the tumor cell targeting peptide depending on target moiety [epidermal growth factor receptor or vimentin in this case] on the tumor cell surface. The polymerized siRNA (poly siRNA) tightly bound to the engineered protein nanocage and formed stable and condensed structure (poly siRNA-protein nanocage complex) without cytotoxicity problem. Furthermore, siRNAs in the condensed complex were effectively protected from endonuclease due to a shielding effect of protein nanocage. In the in vitro treatment of poly siRNA-protein nanocage complex, both of the tumor cell targeting and penetrating peptides were important for efficient delivery of siRNA, and the red fluorescent protein (RFP) expression in RFP-expressing tumor cells was notably suppressed by the delivered siRNA with the complementary sequence to RFP mRNA. It seems that the human ferritin-based protein nanocage is an efficient, stable, and safe tool for siRNA delivery, having a great potential for application to in vivo cancer treatment. The unique feature of protein nanocage is that multiple and functional peptides can be simultaneously and evenly placed and also easily switched on the protein nanocage surface through a simple genetic modification, which is likely to make protein nanocage appropriate for targeted delivery of siRNA to a wide range of cancer cells. Citation Format: Eun Jung Lee, Yoosoo Yang, In-san Kim, Kwangmeyung Kim, Jeewon Lee. Engineered protein nanocage for targeted delivery of siRNA to cancer cells. [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 5519. doi:10.1158/1538-7445.AM2015-5519
P53 Prevents TCR-Dependent Peripheral T-Cell Lymphomagenesis From Chronically Stimulated T Cells.
Authors: Emmanuel Bachy, Alexandra Traverse-Glehen, Sophie Gazzo, Baseggio Lucile, Martine Ffrench, Morgan Taillardet, Gilles Salles, Thierry Defrance, Laurent Genestier
Journal: Blood (2012)
Identification and Characterization of Hemoangiogenic Progenitors during Cynomolgus Monkey ES Cell Differentiation.
Authors: Katsutsugu Umeda, Toshio Heike, Momoko Yoshimoto, Mitsutaka Shiota, Feng Ma, Hirofumi Suemori, Hong Yuan Luo, David H.K. Chui, Ryuzo Torii, Masabumi Shibuya, Norio Nakatsuji, Tatsutoshi Nakahata
Journal: Blood (2004)
PO64VOLUME BASED ANALYSIS OF GLIOBLASTOMAS. PROGRESSION IN IMAGING TECHNIQUES
Authors: Umair Janjua, Deepak Parashar, Paul Sanghera, Vijay Sawlani
Journal: Neuro-Oncology (2015)

INTRODUCTION: Response assessment for Glioblastoma (GBM) is often assessed using the RANO criteria based on linear measurements. However linear measurements may be an inaccurate reflection of volume for tumours with cystic necrotic elements or complex geometric shapes. Automated computer-assisted volumetric analysis may offer a more accurate assessment in such situations. This study explores the differences between linear and volumetric tumour measurements. METHOD: 10 patients with heterogeneously enhancing GBM on 3D post contrast T1 volumetric MRI sequence were selected for this study. Spherical volume of GBM was estimated from 2D measurements (linear) by taking the average of two perpendicular diameters. Volumetric analysis was performed by manually contouring gadolinium enhanced sections of tumour on Agfa PACS. RESULTS: Mean tumour volume was 13.19 cm3 and 10.06 cm3 using linear and volumetric techniques respectively. The nonparametric Wilcoxon signed-rank test (p = 0.092) informs that distributions of 2D Volume and Volumetry are different at the 10% significance level. The one-sided nonparametric sign test (p = 0.05) informs that the 2D Volume is greater than Volumetry for 8 out of 10 observations. CONCLUSION: Linear measurements can over estimate the volume of tumour compared to volumetric analysis. Measuring the change in volume of GBM may provide a more accurate assessment of response than conventional linear measurements used for existing RANO criteria, particularly for necrotic tumours. The benefit of volumetric analysis to assess response in GBM requires prospective validation. Integration of this technique into a prospective study will be discussed.
Myeloproliferative Disease or Myeloid Leukemia Caused by Cbl Mutants in a Mouse Transplantation Model.
Authors: Srinivasa Rao Bandi, Marion Rensinghoff, Rebekka Grundler, Lara Tickenbrock, Gabriele Köhler, Justus Duyster, Wolfgang E Berdel, Hubert Serve, Christian Brandts, Carsten Müller-Tidow
Journal: Blood (2009)
Statistical Validation of a Threshold To Discriminate Flow-Cytometry Minimal Residual Disease (MRD) Levels with Prognostic Significance in Acute Myeloid Leukemia (AML).
Authors: Francesco Buccisano, Luca Maurillo, Valter Gattei, Giovanni Del Poeta, Maria Ilaria Del Principe, Paola Panetta, Daniela Fraboni, Maria Irno Consalvo, Licia Ottaviani, Daniela Renzi, Sabrina Faccia, Chiara Sarlo, Francesco Lo Coco, Sergio Amadori, Adriano Venditti
Journal: Blood (2006)
PKM2 as a biomarker for sensitivity to oxaliplatin-based chemotherapy in metastatic colorectal cancer (mCRC).
Authors: C. Papadaki, Z. Saridaki, M. Tzardi, M. Sfakianaki, G. Sfakiotaki, M. Trypaki, I. Messaritakis, D. Mavroudis, V. Georgoulias, I. Sougklakos
Journal: Journal of Clinical Oncology (2011)

434 Background: Tumour cells have been shown to express exclusively the embryonic M2 isoform of pyruvate kinase (PKM2), which is a key enzyme that regulates aerobic glycolysis in tumor cells. Use of RNA interfering (RNAi) targeting PKM2 significantly inhibits tumor growth when combined with cisplatin in xenograft models. We evaluated the predictive significance of PKM2 in patients with mCRC treated with oxaliplatin- based chemotherapy in the first-line setting. Methods: FFPE primary tumors from 140 mCRC patients were analyzed for PKM2 mRNA expression by RT-qPCR. The analysis was performed with a set of primers and probes which amplify only the M2 isoform. Results: The patients' characteristics were all typical for mCRC (median age 65 years, 61% males, 75% colon cancer 25% rectal cancer, 41% undifferentiated tumors, 21% mucinous features). PKM2 was successfully amplified in all specimens. Time to tumor progression (TTP) was significantly lower in patients with overexpression of PKM2 (6.7 vs. 9.1 months for high and low expression, respectively, p=0.004). Similarly, median overall survival (mOS) was significantly decreased in patients with upregulation of PKM2 (21.9 vs. 30.2 months for high and low expression, respectively, p=0.004). Multivariate analysis revealed PKM2 high mRNA expression (HR: 1.7, p=0.005) and the presence of undifferantited tumors (HR: 2.2, p&lt;0.0001) as independent prognostic factors for decreased TTP. Similarly, PKM2 high mRNA expression (HR: 1.8, p=0.005) and the presence of undifferantited tumors (HR: 2.5, p&lt;0.0001) were revealed as independent prognostic factors for decreased mOS. Conclusions: These results provide evidence that the PKM2 mRNA expression could be used as a predictive factor for sensitivity to oxaliplatin-based chemotherapy. The results should be validated prospectively in an independent patient cohort. No significant financial relationships to disclose.
In Vitro Characterization of the Neutralization of Unfractionated Heparin and Low Molecular Weight Heparin by Novel Salicylamide Derivatives.
Authors: Walter Jeske, Aleah Brubaker, Dahui Liu, Trevor Young, Debra Hoppensteadt, Omer Iqbal, Jawed Fareed, Jeanine M. Walenga, Mamdouh Bakhos
Journal: Blood (2007)
Inducible gene-targeting reveals critical roles for VEGFR-1 and VEGFR-2 during early postnatal development in the mouse
Authors: Megan E. Baldwin, Xiao Huan Liang, Anja Ruchatz, Johanna Busch, Zhenyu Gu, Meron Roose-Girma, Christine Olsson, Sharon Erickson, Napoleone Ferrara, Hans-Peter Gerber
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

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Vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2, also known as fms-like tyrosine kinase (Flt-1) and fetal liver kinase 1 (Flk-1)/kinase insert domain receptor (KDR) respectively, are receptor tyrosine kinases that bind with high affinities to members of the VEGF family. Conventional gene-targeting strategies demonstrated the essential roles of VEGFR-1 and VEGFR-2 during early embryonic development, as mouse embryos that are null for either receptor die between days 8.5 and 9.5 due to profound defects in angiogenesis and formation of a functional cardiovascular system. However, due to the early embryonic lethality of VEGFR-1 and VEGFR-2 null mice, the role of these receptors during early postnatal life and in the adult has remained unclear. To assess the role of VEGFR-1 and VEGFR-2 in postnatal development, we have utilized the Cre-LoxP system to generate conditional knockouts of either receptor. VEGFR-1-LoxP and VEGFR-2-LoxP mice, in which the first coding exon and a region of the promotor of each gene is flanked by LoxP sites, were bred with Mx-1Cre mice in which the expression of Cre-recombinase is driven by an interferon (IFN)- α inducible gene promoter. In the resulting VEGFR-1-LoxP.Mx1-Cre and VEGFR-2-LoxP.Mx1-Cre mice, induction of Cre-recombinase expression with IFN- α (or the IFN- α inducer polyinosinic-polycytidylic acid) results in LoxP recombination with 95% efficiency in bone marrow, liver and spleen, and 50% or less efficiency in various organs, including kidney, heart and lung. IFN- α adminstration to newborn VEGFR-1-LoxP(+/+).Mx1-Cre(+) and VEGFR-2-LoxP(+/+).Mx1-Cre(+) adversely affected body mass gain and survival compared to wild-type controls, demonstrating a critical role for both receptors during early postnatal development. In contrast, in these mice, short term genetic ablation of VEGFR-1 and VEGFR-2 in the liver, bone marrow and spleen, beginning at 6 weeks of age did not induce any significant changes in total body or organ mass, indicating that VEGFR-1 and VEGFR-2 are dispensible for survival and maintenance of organ function in adult mice for up to 4 weeks following induction of the knock-out. Data will be presented to illustrate and contrast the consequences of VEGFR-1 and VEGFR-2 genetic ablation in various organs and tissues of newborn and adult VEGFR-1-LoxP.Mx1-Cre and VEGFR-2-LoxP.Mx1-Cre mice injected with IFN- α.