tbuckley/cabot-search huggingface dataset:
Abstract 2383: IL-6 and RANTES mediate the cross-talk between tumor cells and CAFs in the esophageal tumor microenvironment
Authors: Tatiana A. Karakasheva, Monica Soni, Todd Waldron, Anil K. Rustgi
Journal: Cancer Research (2015)

Abstract Desmoplasia, or deposition of connective tissue proper in the stroma, is a key characteristic of esophageal squamous cell carcinoma (ESCC). The cellular component of connective tissue proper is comprised of fibroblasts, and cancer-associated fibroblasts (CAFs) are widely recognized as a major constituent of the tumor microenvironment (TME). The purpose of this study was to identify tumor-promoting factors that are secreted as a result of the crosstalk between CAFs and tumor cells in ESCC. We have performed a comprehensive cytokine array and found that IL-6 and RANTES (also known as CCL5) are significantly overexpressed in conditioned media from co-culture of esophageal CAFs and ESCC cells, compared to mono-culture. Both proteins are known to play important roles in the development of multiple types of cancer, mostly via activation of the STAT3 signaling pathway. We have demonstrated that co-culture with fibroblasts prompts the ESCC cells to acquire a more mesenchymal phenotype and express potent mediators of cell migration and invasion, such as matricellular proteins (periostin, fibrillin, osteonectin) and hepatocellular growth factor (HGF). Furthermore, knockdown of IL-6 suppresses invasiveness and proliferation of human ESCC cells in our 3D organotypic culture model. We have also performed staining of tissue samples from ESCC patients and found that, compared to normal esophagus, expression of IL-6 and RANTES is enhanced in ESCC in both epithelial cells and fibroblasts. In summary, our findings indicate that IL-6 and RANTES are responsible for migration and invasion of ESCC cells promoted by CAFs in the tumor microenvironment. This is the first report of such a dual induction of these specific cytokines in ESCC, and it provides a rationale for dual inhibition of IL-6 and RANTES as novel therapy for ESCC, and possibly other types of cancer. Supported by NCI P01 CA098101. Citation Format: Tatiana A. Karakasheva, Monica Soni, Todd Waldron, Anil K. Rustgi. IL-6 and RANTES mediate the cross-talk between tumor cells and CAFs in the esophageal tumor microenvironment. [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 2383. doi:10.1158/1538-7445.AM2015-2383
PX-171-004, An Ongoing Open-Label, Phase II Study of Single-Agent Carfilzomib (CFZ) in Patients with Relapsed or Refractory Myeloma (MM); Updated Results From the Bortezomib-Treated Cohort.
Authors: David Siegel, Luhua Wang, Robert Z Orlowski, Jonathan L. Kaufman, A. Keith Stewart, Vishal Kukreti, Melissa Alsina, Andrzej J Jakubowiak, Sundar Jagannath, Kevin T. McDonagh, Andrew Belch, Nizar J Bahlis, Chaim Shustik, Mai H. Le, Lori Kunkel, Mark K Bennett, Michael Kauffman, Ravi Vij
Journal: Blood (2009)
PTH-013 Comparison of the first and second round of colorectal cancer screening in northeast England: Abstract PTH-013
Authors: C J Rees, M Rutter, N J Dempsey, G Waddup, M C Ritchie, J N Singh, D L Nylander, J E Painter, I Ward, G M Clifford
Journal: Gut (2010)

<h3>Introduction</h3> South of Tyne and Tees bowel cancer screening centres commenced screening in February 2007 as first wave centres. They serve a combined population of 1.5 million. The aims of the prospective audit were 1. To analyse the findings at colonoscopy among individuals with positive FOB in round 2 of screening and correlate this with their own results from round 1 of screening and 2. To compare findings at the first and second round of screening. <h3>Methods</h3> A prospective audit of all patients with a positive FOB screened in round one and two and undergoing colonoscopy was undertaken. For individuals undergoing the second round of screening a comparison was made with their first round of screening 2 years earlier. Individuals with an abnormal FOB result (5/6 positive windows) or a weak positive result (initial test indeterminate and subsequent strong positive or indeterminate) are invited for colonoscopy. Individuals with an initial indeterminate result then two normal FOB9s are invited for repeat FOB testing in 2 years time. <h3>Results</h3> 1490 patents were colonoscoped between 2007 and 2009 in the first round of screening and subsequently 118 patients since the second round commenced in April 2009. Of the 118 scoped as part of their second round, 109 had a negative FOB in round 1, of which six were diagnosed with cancer and nine with high-risk polyps in round 2. A further 29 had low or intermediate risk polyps, 21 abnormal not polyps and 34 were normal. Of the six patients who had weak positive then 2 normals in round 1, 3 had low or intermediate risk polyps, 1 abnormal not polyps and 2 normal. Of 3 patients with positive FOBs (colonoscoped) in round 1, 1 had low risk polyps and 2 were abnormal but not polyps in round 2. Abstract 013 compares overall findings of screening in round 1 and 2 demonstrating that cancer diagnosis was more likely in round 1. <h3>Conclusion</h3> Round 2 of screening demonstrated a high yield of pathology including six patients with cancer and nine with high-risk polyps. All of these patients had completely negative FOBs in round 1. A diagnosis of cancer was more likely in round one. Abstract submitted on behalf of the Northern Region Endoscopy Group.
Movement Initiation Signals in Mouse Whisker Motor Cortex
Authors: Varun Sreenivasan, Vahid Esmaeili, Taro Kiritani, Katia Galan, Sylvain Crochet, Carl C.H. Petersen
Journal: Neuron (2016)

Frontal cortex plays a central role in the control of voluntary movements, which are typically guided by sensory input. Here, we investigate the function of mouse whisker primary motor cortex (wM1), a frontal region defined by dense innervation from whisker primary somatosensory cortex (wS1). Optogenetic stimulation of wM1 evokes rhythmic whisker protraction (whisking), whereas optogenetic inactivation of wM1 suppresses initiation of whisking. Whole-cell membrane potential recordings and silicon probe recordings of action potentials reveal layer-specific neuronal activity in wM1 at movement initiation, and encoding of fast and slow parameters of movements during whisking. Interestingly, optogenetic inactivation of wS1 caused hyperpolarization and reduced firing in wM1, together with reduced whisking. Optogenetic stimulation of wS1 drove activity in wM1 with complex dynamics, as well as evoking long-latency, wM1-dependent whisking. Our results advance understanding of a well-defined frontal region and point to an important role for sensory input in controlling motor cortex.
Total Anomalous Pulmonary Venous Connection
Authors: Guocheng Shi, Zhongqun Zhu, Jimei Chen, Yanqiu Ou, Haifa Hong, Zhiqiang Nie, Haibo Zhang, Xiaoqing Liu, Jinghao Zheng, Qi Sun, Jinfen Liu, Huiwen Chen, Jian Zhuang
Journal: Circulation (2016)

Total anomalous pulmonary venous connection (TAPVC) is a rare form of congenital heart disease. This study describes current surgical treatment strategies and experiences in a cohort of patients from 2 congenital cardiac centers in Shanghai and Guangdong in China.This retrospective study included 768 patients operated on between 2005 and 2014. Although most patients (n=690) underwent conventional repair, a sutureless technique was used in 10% (n=78) of cases. A multilevel mixed-effects parametric survival model and a competing-risk analysis were used to analyze associated risk factors for death and recurrent pulmonary venous obstruction (PVO), respectively. Kaplan-Meier analysis was used to analyze the overall survival. The Nelson-Aalen cumulative risk curve was used to compare distributions of time with recurrent PVO.The mean surgical age and weight were 214.9±39.2 days and 5.4±3.6 kg, respectively. Obstructed TAPVC (PVO) was documented in 192 (25%) of the 768 patients. There were 38 intraoperative deaths and 13 late deaths. A younger age at the time of repair (P=0.001), mixed (P=0.004) and infracardiac (P=0.035) TAPVC, preoperative PVO (P=0.027), prolonged cardiopulmonary bypass time (P<0.001), and longer duration of ventilation (P=0.028) were associated with mortality. The median follow-up was 23.2 months (range; 1-112 months). Among the 717 survivors, recurrent PVO was observed in 111 patients (15%). Associated risk factors for recurrent PVO included preoperative PVO (P<0.001), infracardiac TAPVC (P<0.001), mixed TAPVC (P=0.013), and prolonged cardiopulmonary bypass time (P<0.001). Sutureless technique was associated with a lower restenosis rate compared with conventional repair in patients with preoperative PVO (P=0.038), except in newborn patients (P=0.443). Reintervention for restenosis was performed in 24 patients. The function of most survivors (91%) was classified according to the New York Heart Association as functional class I or II.Surgical correction in patients with TAPVC with a biventricular anatomy can achieve an acceptable outcome. Risk factors such as a younger age at the time of repair, infracardiac and mixed TAPVC, and preoperative PVO were associated with a poorer prognosis.
Abstract 5143: Rats heterozygous for Pten develop fibroadenoma and adenocarcinoma arising from the mammary gland
Authors: Aaron M. McCoy, Bala Manickam, Lara Reid, Edward Weinstein, Xiaoxia Cui
Journal: Cancer Research (2015)

Abstract To further characterize the function of the tumor suppressor Pten in the role of tumorigenesis we have created a colony of Pten mutant Sprague Dawley (SD) rats. Utilizing zinc finger nuclease technology we introduced a 7bp deletion in Exon 7 of the Pten gene, creating a frameshift mutation and an early stop codon. Pten homozygous null animals are not viable so a colony of heterozygous animals is maintained. Spontaneous tumors of the mammary gland arise in these animals and were removed for staining and pathological analysis. We describe briefly the creation of this model and preliminary genotypic and proteomic characterization. Further we describe pathological observations made on tumor tissues removed from aging Pten heterozygous animals. We have confirmed a reduction in Pten expression by Western Blot utilizing a monoclonal antibody targeting a central locus in the protein. Heterozygous Pten animals develop spontaneous tumors of the mammary gland which were removed if animals demonstrated deteriorating health or any condition within our Humane Care and Use guidelines. Thirty six tissues from 16 animals were submitted for histopathological analysis. Eight of the animals were male, 8 of the animals were female and had a mean lifespan of 159 days (165 male, 153 female). Remaining consistent with human breast cancer incidence in women below 30 years of age, the most common lesion observed is a benign fibroadenoma (30/36 samples). The malignant adenocarcinoma was observed in 5/36 samples submitted. Fibroadenoma only lesions were observed in 12 of the 16 rats while both fibroadenoma and adenocarcinoma was observed in 4 of the 16 rats. Taken together we believe that a Pten heterozygous rat provides an additional tool for the elucidation of the role of Pten in human cancers. This model may also be useful in the study of neurological disorders such as Autism, Parkinson's disease, Alzheimer's disease, obesity, cardiovascular disease, and diabetes. Mutations in Pten strongly correlate with several human disorders including Cowden syndrome, Bannayan-Zonana syndrome, and Lhermitte-Duclos disease. These disorders result in a tumor pathologies including an increased risk for breast cancers. Citation Format: Aaron M. McCoy, Bala Manickam, Lara Reid, Edward Weinstein, Xiaoxia Cui. Rats heterozygous for Pten develop fibroadenoma and adenocarcinoma arising from the mammary gland. [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 5143. doi:10.1158/1538-7445.AM2015-5143
Are all sport activities equal? A systematic review of how youth psychosocial experiences vary across differing sport activities
Authors: M Blair Evans, Veronica Allan, Karl Erickson, Luc J Martin, Ross Budziszewski, Jean Côté
Journal: British Journal of Sports Medicine (2016)

Objective Models of sport development often support the assumption that young athletes' psychosocial experiences differ as a result of seemingly minor variations in how their sport activities are designed (eg, participating in team or individual sport; sampling many sports or specialising at an early age). This review was conducted to systematically search sport literature and explore how the design of sport activities relates to psychosocial outcomes. Design Systematic search, followed by data extraction and synthesis. The Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were applied and a coding sheet was used to extract article information and code for risk of bias. Data sources Academic databases and manual search of peer-reviewed journals. Eligibility criteria for selecting studies Search criteria determined eligibility primarily based on the sample (eg, ages 7 through 17 years) and study design (eg, measured psychosocial constructs). Results 35 studies were located and were classified within three categories: (1) sport types, (2) sport settings, and (3) individual patterns of sport involvement. These studies represented a wide range of scores when assessed for risk of bias and involved an array of psychosocial constructs, with the most prevalent investigations predicting outcomes such as youth development, self-esteem and depression by comparing (1) team or individual sport participants and (2) youth with varying amounts of sport involvement. Summary/conclusion As variations in sport activities impact youth sport experiences, it is vital for researchers to carefully describe and study these factors, while practitioners may use the current findings when designing youth sport programmes.
The Anti-CD30 Monoclonal Antibody SGN-30 Inhibits Hodgkins Disease Growth and Sensitizes Cells to Established Chemotherapeutics.
Authors: Charles G. Cerveny, Che-Leung Law, Renee S. McCormick, Joel S. Lenox, Kevin J. Hamblett, Lori E. Westendorf, Andrew K. Yamane, Joseph M. Petroziello, Joseph A. Francisco, Alan F. Wahl
Journal: Blood (2004)
Opioid manufacturer bribed doctors to prescribe fentanyl inappropriately, US says
Authors: Owen Dyer
Journal: BMJ (2016)

Arizona drug manufacturer Insys Therapeutics sold its fentanyl spray, Subsys, through a business model based on bribing doctors to prescribe off-label and lying to insurers about patients’ medical histories, according to a federal indictment against six former Insys executives, including the former chief executive and president, Michael Babich.1

The six, who left the company last year, have been arrested and charged with racketeering under a law normally used to tackle organized crime. They are also charged with violating the federal anti-kickback statute and with mail or wire fraud in their promotion of Subsys. The racketeering and fraud charges each carry a sentence of up to 20 years in prison.

Detailed allegations about the company’s relationship with 10 medical practitioners are laid out in the indictment. The 10 are not named, …
Development of a mathematical model of intraperitoneal/intravenous infusion of taxanes.
Authors: Y. Miyagi, K. Fujiwara, K. Ito, Y. Miyagi, T. Takano, S. Nagao, N. Yaegashi, T. Oda, T. Miyake, K. Miyake
Journal: Journal of Clinical Oncology (2011)

e15585 Background: For ovarian cancer patients, it remains unclear whether paclitaxel (T) or docetaxel (D) should be administered intraperitoneally (IP) or intravenously (IV). Because it is virtually impossible to measure the actual tissue concentration in peripheral organs, we have developed a three-compartment mathematical model for both IP and IV administration to estimate the pharmacological information in the serum (S), the peritoneal cavity (CV), and the peripheral space (PRH). Methods: A model with simultaneous differential equations was created and solved to fit the sample data based on reports of pharmacodynamics in both S and CV regarding T and D, respectively. Results: The rate constants of [T,D] for CV to S, S to CV, S to PRH, PRH to S, CV to PRH, PRH to CV, and elimination were [0.01, 0.095], [0.0001, 0.00005], [25, 7], [0.101, 0.2], [150, 161], [0.1, 70], [21, 45] (/hr), respectively. By calculation, the AUC value in S was identical both IP and IV, and the values in both CV and PRH were higher IP. The AUC ratio of T/D in S was 6.4. The AUC ratios of T/D in CV was 0.03 and 0.08 by IP and IV, respectively. The ratios of total amount of T/D in PRH was 13.5 and 54.7 by IP and IV, respectively. Conclusions: A mathematical model of IP/IV administration of taxanes demonstrated the feasibility of T IP for the extraperitoneal lesions, and D IP for the intraperitoneal lesions.
In vivo Tissue Cholesterol Efflux is Impaired in Carriers of Mutations in APOA1 and ABCA1
Authors: Adriaan G. Holleboom, Remco Franssen, Lily Jakulj, Julie Decaris, Menno Vergeer, Joris Koetsveld, Marc K. Hellerstein, John J. Kastelein, Albert K. Groen, Scott M. Turner, Erik S. Stroes
Journal: Circulation (2010)
Abstract 1726: CRM1 is overexpressed in lung tumorigenesis and represents an adjuvant target for lung cancer treatment
Authors: Weimin Gao, Chuanwen Lu, Lixia Chen, Phouthone Keohavong
Journal: Cancer Research (2015)

Abstract In spite of extensive investigations, the molecular mechanisms of lung tumorigenesis have not been completely understood, and the effective therapy for lung cancer is in great demand. Studies have shown that chromosome region maintenance 1 (CRM1), a nuclear export receptor for various cancer-associated ‘cargo’ proteins, overexpressed in several human cancers. The objectives of the present study are to evaluate the involvement of CRM1 in lung carcinogenesis and lung cancer treatment. First, we have analyzed the importance of CRM1 overexpression in lung cancer development. We showed that CRM1 was overexpressed in lung tumor tissues from lung cancer patients and lung adenocarcinoma in mice induced by a tobacco carcinogen, as well as lung cancer cell lines. The increased CRM1 expression levels in these lung cancer tissues and cells were associated with an increased phosphorylation level at threonine residue 55 of the p53 protein. Furthermore, CRM1 overexpression in lung cancer cells seemed to be p53-dependent. Stable overexpression of CRM1 in BEAS-2B cells led to malignant cellular transformation and p53 cytoplasmic localization. Moreover, as compared to A549 cells, cancer-related genes significantly altered in A549 cells with stable CRM1 knockdown. Second, we have evaluated targeting CRM1 as an adjuvant therapy for lung cancer treatment using both in vitro and in vivo models. We found that CRM1-siRNA could inhibit A549 cell growth and A549 cells with stable CRM1 knockdown showed more pronounced cytotoxic effects to cisplatin than A549 cells. In addition, A549 cells treated with cisplatin and a low non-toxic dose of leptomycin B (a CRM1 inhibitor) had a remarkably enhanced cytotoxicity compared to cisplatin. This increased therapeutic effect from leptomycin B and cisplatin was further validated using an in vivo xenograft mouse model. The findings of this study reveal the significance of CRM1 in lung carcinogenesis and lung cancer adjuvant therapy. Citation Format: Weimin Gao, Chuanwen Lu, Lixia Chen, Phouthone Keohavong. CRM1 is overexpressed in lung tumorigenesis and represents an adjuvant target for lung cancer treatment. [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 1726. doi:10.1158/1538-7445.AM2015-1726
Use of The Mini Nutritional Assessment to determine the Prevalence of Malnutrition And Cachexia In Patients Undergoing Surgery For Colorectal Carcinoma
Authors: A. Daniele, R. Divella, R. De Luca, S. Montemurro, E. Ruggieri, C. Caliandro, V. Cilifrese, F. Giotta, M. Lioce, M.T. Casadibari, R. Mallamaci, P. Casamassima, E. Savino, A. Atlante, M. Cattedra, I. Abbate
Journal: Annals of Oncology (2015)
Potent Antineoplastic Activity of Two Inhibitors of Lymphoid Enhancer Binding Factor-1 (LEF-1) in Chronic Lymphocytic Leukemia (B-CLL).
Authors: Rajesh Kumar Gandhirajan, Iris Gehrke, Alexandra Filipovich, Julian Paesler, Regina Razavi, Felix Erdfelder, Magdalena Hertweck, Simon Jonas Poll-Wolbeck, Sabrina Uhrmacher, Axel Schlösser, Esther Katharin Schmitt, Guenter Plickert, Michael Hallek, Karl Anton Kreuzer
Journal: Blood (2009)
Expression of cancer testis (CT) antigens in human BRCA-associated breast cancers: Potential targets for immunoprevention?
Authors: S. Adams, L. Greeder, E. Reich, Y. Shao, S. Demaria, A. Jungbluth
Journal: Journal of Clinical Oncology (2011)

e11098 Background: Novel breast cancer risk-reducing strategies for individuals with germline mutations of the BRCA1 and/or BRCA2 genes are urgently needed. Identification of antigenic targets which are expressed in early cancers, in situ or invasive, but absent in normal breast epithelium of these high-risk individuals could provide the basis for the development of effective immunoprohylactic strategies. Cancer Testes (CT) antigens are potential candidates because their expression is restricted to tumors and accumulating data suggest that they play important roles in cellular proliferation, stem cell function and carcinogenesis of at least some tumors. The objective of this study was to examine the expression of CT antigens and their frequency in BRCA-associated breast cancers. Methods: Archived breast cancer tissues (n=26) as well as morphologically normal breast tissues (n=7) from women carrying deleterious BRCA 1 and or 2 mutations were obtained for antigen expression analysis by immunohistochemistry. Expression of the following CT antigens was examined: MAGE-A1, MAGE-A3, MAGE-A4, MAGE-C1.CT7, NY-ESO-1, MAGE-C2/CT10 and GAGE. Results: CT antigens were expressed in 61.5% (16/26) of BRCA-associated cancers. 50% (13/26) of tumors expressed two or more CT antigens; three cancers expressed all seven CT antigens. CT antigens were expressed across all tumor types and stages including DCIS. In contrast, none of the CT antigens were expressed in adjacent or contralateral normal breast epithelium (p<0.01). Conclusions: We report a high CT antigen expression rate in BRCA-associated breast cancer as well as the lack of expression of these antigens in benign breast tissue of carriers, identifying CT antigens as potential vaccine targets for breast cancer prevention in these high-risk individuals.
Interim FDG PET Imaging in CALGB 50203 Trial of Stage I/II Non-Bulky Hodgkin Lymphoma: Would Using Combined PET and CT Criteria Better Predict Response Than Each Test Alone?,
Authors: Lale Kostakoglu, Heiko Schoder, Nathan Hall, David J. Straus, Jeffrey L Johnson, Lawrence Schwartz, Ann LaCasce, Sin-Ho Jung, Nancy L. Bartlett, George P. Canellos, Bruce D. Cheson
Journal: Blood (2011)