tbuckley/cabot-search huggingface dataset:
Abstract 3927: The presence of COX-2 and tumor-associated macrophages as a prognostic marker for invasive breast carcinoma patients
Authors: Karla Esbona, Sandeep Saha, Yanyao Yi, Menggang Yu, Kari Wisinski, Lee G. Wilke, Patricia J. Keely
Journal: Cancer Research (2016)

Abstract Inflammation is an important mediator of tumor progression. The objective of this study was to assess whether the tissue localization of COX-2 and tumor-associated macrophages were associated with clinicopathological features of invasive carcinoma, including collagen deposition and patient survival outcome. A tumor microarray (TMA) of 371 biopsy specimens from patients with invasive breast carcinoma was analyzed for expression of high levels of COX-2, and the macrophage markers CD68 and CD163 in either the tumor nest (TN) or the tumor-associated stroma (TS). The study population for this TMA was female patients, 18 to 80 years of age with a median follow up of 8.4 years. Survival tables were calculated according to the Kaplan-Meier method. We found that elevated collagen deposition was associated with high stromal expression of COX-2 (P &amp;lt; 0.0001); however, the amount of collagen deposition was not a predictor for survival outcome. In order to better analyze patient data, samples were divided into quartiles based on their levels of COX-2 expression and/or macrophage infiltration. Tumor nests with high COX-2 expression had worse patient outcome (P = 0.011). One possible mechanism for this is COX-2 dependent recruitment of macrophages to the tumor microenvironment, supported by our finding of high infiltration of CD68+ macrophages in the TS, and CD163+ macrophages in both TN and TS. This recruitment of macrophages was associated with worse overall survival (OS). Furthermore, patient survival was worsened even more if macrophages expressed COX-2, suggesting positive amplification of COX-2 signaling via macrophage recruitment. This notion is further established by the finding of high presence of CD163+ macrophages in the TN as an independent prognostic factor as revealed by multivariate analysis (P &amp;lt; 0.0001, HR = 4.67). These results suggest that in invasive carcinoma the localization of inflammatory markers within the tumor are biomarkers for patient survival outcome. Therefore, we propose that these patients may benefit from therapy with a selective COX-2 inhibitor such as celecoxib. Citation Format: Karla Esbona, Sandeep Saha, Yanyao Yi, Menggang Yu, Kari Wisinski, Lee G. Wilke, Patricia J. Keely. The presence of COX-2 and tumor-associated macrophages as a prognostic marker for invasive breast carcinoma patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3927.
GRM1 is An Androgen-Regulated Gene and its Expression Correlates with Prostate Cancer Progression in Pre-Clinical Models
Authors: Mojgan Shourideh, Gissou Azabdaftari, Kristopher Attwood, Adam DePriest, Kristine M Wadosky, Bryan M Gillard, Ellen Karasik, Hannelore Heemers, Natasha Kyprianou, Irwin H Gelman, Eva Corey, Robert L Vessella, James L Mohler, Shahriar Koochekpour
Journal: Clinical Cancer Research (2016)

We recently demonstrated that glutamate receptor GRM1 was expressed at high levels in castration-resistant prostate cancer (CR-PCa) tissues and cells. Herein, we determined the relationship between GRM1 and AR, PSA, and tumor growth, remission, and recurrence in preclinical PCa models. The effect of alterations in GRM1 expression was also investigated on PCa cell growth, migration and invasion.
A phase II study to assess vismodegib in the neoadjuvant treatment of locally advanced basal cell carcinoma (laBCC): The Vismodegib Neoadjuvant (VISMONEO) study.
Authors: Laurent Mortier, Philippe Saiag, Marie Thérèse Leccia, Abdelkader Mahmoudi, Liubinka Mirakovska, Damia Meddour, Alain Duhamel, Xavier Mirabel, Pierre Guerreschi
Journal: Journal of Clinical Oncology (2014)

TPS9104 Background: BCC is the most common skin malignancy. Surgery cures most cases, but a few patients may exhibit progression to life-threatening, unresectable, locally advanced disease or metastatic tumors and there is no standard therapy for this condition. Vismodegib is a small molecule antagonist of the Hedgehog signalling pathway newly approved in this indication. It showed in a phase II study (ERIVANCE BCC), a tumor response rate of 43% (95%CI: 31 to 56; p<0.001) in laBCC (complete responses 21%). We intend to assess vismodegib in the neo-adjuvant treatment of BCC aiming at reducing the BCC size which will allow a lower surgical stage and preserve the functional and the aesthetic appearance of the affected area. Methods: This is an open-label, non-comparative, multicenter, phase II study of vismodegib in patients with laBCC conducted in 33 centers in France. Main eligibility criteria are: age≥ 18 years, histologically confirmed diagnosis of laBCC, BCC with a diameter ≥ 3 cm in areas of intermediate risk of tumor recurrence and ≥ 2 cm in areas of higher risk of tumor recurrence, measurable and/or non-measurable disease, adequate liver and hematological functions. Enrolled patients receive vismodegib 150 mg once-daily po continuously. One cycle of therapy is defined as 28 days of treatment. All patients receive study drug until best overall response, within a maximum treatment period of 10 months. The primary endpoint is the proportion of BCC patients with a down-staging of the initial surgical stage following vismodegib neoadjuvant treatment. Surgical stage, validated by the Reconstructive Surgery teams of three University Hospitals in France, includes tumor size and surgical procedure planned. Secondary endpoints are safety, clinical benefit (assessed by an independent panel of experts), quality of life (Skindex-16 Questionnaire at baseline, after Cycle 1, Cycle 3, Cycle 6, end of treatment), and medico-economical assessment. A total of 50 patients will be recruited; they will be followed-up for 3 years after surgery. Clinical trial information: 2013-004338-13.
Medical Care When Memory Fails
Authors: Eric B. Larson
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Circadian and Septadian Variation in the Occurrence of Acute Myocardial Infarction in a Chinese Population
Authors: Zhou Rui-Hai, Xi Bin, Gao Hai-Qing, Liu Xiang-Qun, Li Yong-Sheng, Cao Kong-Jing, Lu Hui-Ming, Zhao Chang-Qin, Li Xiu-Qin
Journal: Circulation (1998)

To investigate whether circadian or any other temporal pattern(s) exist in the occurrence of acute myocardial infarction (AMI) in a Chinese population, we analyzed 428 patients with confirmed AMI for temporal patterns of AMI occurrence. The patients admitted to the Affiliated Hospital of Shandong Medical University during 1991-95 were from Jinan, the capital city of Shandong Province of China, which has a population of 2.5 million. The chi-square test for goodness of fit was used to test the difference among the frequencies of AMI occurrence in 4 equal intervals (O1.00-07.00 h, 07.00-13.00 h, 13.00-19.00 h, 19.00-01.00 h) during the day and among those on 7 days during the week. The results showed that AMI occurrence exhibited significant circadian (p<0.001) and septadian (day of the week) (p=0.046) periodicity, with a peak at O1.00-07.00 h and a trough at 13.00-19.00 h during the day, and a peak on Saturday and a trough on Wednesday during the week. The peak to trough ratio of risk was 2.7 during the day and 2.1 during the week. It is concluded that there were circadian and septadian biorhythms in AMI occurrence in the Chinese population and that these were different from those observed in Western populations. Further investigation of the underlying mechanisms may shed further light on the trigger mechanisms of AMI and thus be helpful in the prevention and treatment of AMI. (Jpn Circ J 1998; 62: 190 - 192)
IL-21 Enhances Natural Killer Cell Response to Cetuximab-Coated Pancreatic Tumor Cells
Authors: Elizabeth L. McMichael, Alena Cristina Jaime-Ramirez, Kristan D. Guenterberg, Eric Luedke, Lakhvir S. Atwal, Amanda R. Campbell, Zhiwei Hu, Armika S. Tatum, Sri Vidya Kondadasula, Xiaokui Mo, Susheela Tridandapani, Mark Bloomston, E. Christopher Ellison, Terence M. Williams, Tanios Bekaii-Saab, William E. Carson
Journal: Clinical Cancer Research (2016)

Alternative strategies to EGFR blockage by mAbs is necessary to improve the efficacy of therapy in patients with locally advanced or metastatic pancreatic cancer. One such strategy includes the use of NK cells to clear cetuximab-coated tumor cells, as need for novel therapeutic approaches to enhance the efficacy of cetuximab is evident. We show that IL-21 enhances NK cell-mediated effector functions against cetuximab-coated pancreatic tumor cells irrespective of KRAS mutation status.NK cells from normal donors or donors with pancreatic cancer were used to assess ADCC, IFN-γ release, and T-cell chemotaxis toward human pancreatic cancer cell lines. The in vivo efficacy of IL-21 in combination with cetuximab was evaluated in a subcutaneous and intraperitoneal model of pancreatic cancer.NK cell lysis of cetuximab-coated wild-type and mutant kras pancreatic cancer cell lines were significantly higher following NK cell IL-21 treatment. In response to cetuximab-coated pancreatic tumor cells, IL-21-treated NK cells secreted significantly higher levels of IFN-γ and chemokines, increased chemotaxis of T cells, and enhanced NK cell signal transduction via activation of ERK and STAT1. Treatment of mice bearing subcutaneous or intraperitoneal EGFR-positive pancreatic tumor xenografts with mIL-21 and cetuximab led to significant inhibition of tumor growth, a result further enhanced by the addition of gemcitabine.These results suggest that cetuximab treatment in combination with IL-21 adjuvant therapy in patients with EGFR-positive pancreatic cancer results in significant NK cell activation, irrespective of KRAS mutation status, and may be a potential therapeutic strategy. Clin Cancer Res; 23(2); 489-502. ©2016 AACR.
Abstract 605: Building better cell models for screening oncology compounds
Authors: David M. Evans, Michael Selby, Rene Delosh, Julie Laudeman, Chad Ogle, Russell Reinhart, Thomas Silvers, Ralph E. Parchment, Beverly Teicher
Journal: Cancer Research (2016)

Abstract The NCI60 screen is a valuable compound screening service offered to researchers for 20+ years. The screen allows the submission of small molecules, biologics and natural products for testing in the NCI60 cell line panel (60 cell lines covering 9 major tumor types). Sophisticated tools such as COMPARE allow stratification of compounds based on pattern of cell line response and these tools elucidated several compounds with differential specificity for a disease type (e.g. breast cancer over melanoma). Since inception the NCI60 screen has been performed in 96-well plates on monolayer cultures of cells. SulfoRhodamine B was used to measure cell viability after a 48h exposure to the compounds at either a single concentration or 5 point concentration response assay. However, recent work has suggested that cells in 3D culture may respond differently to compounds than in 2D. 3D culture systems produce tumor cell spheroids that exhibit features seen in vivo including greater cell-cell contact, and gradients of nutrients and oxygen between the periphery and the center of the spheroid. We sought to optimize the NCI60 cells for use in a 3D spheroid model that would be suitable for screening compounds. By varying NCI60 cell plating density and incubation times, we optimized the formation of spheroids of a given diameter (500um) in Ultra Low Attachment (ULA) plates. Spheroids were imaged using a high content imaging plate reader and classified into 4 categories based on their apparent morphologies. Comparisons were made in drug sensitivity between 2D and 3D model systems using the NCI60 and cells derived from PDX samples. Data on the optimal cell densities of the NCI60 lines used for spheroid formation as well as concentration response effects of select agents compared in 2D and 3D models are presented. These data will allow others to rapidly utilize these 3D models to determine the differential drug sensitivity of select cell types. Funded by NCI Contract No. HHSN261200800001E. Citation Format: David M. Evans, Michael Selby, Rene Delosh, Julie Laudeman, Chad Ogle, Russell Reinhart, Thomas Silvers, Ralph E. Parchment, Beverly Teicher. Building better cell models for screening oncology compounds. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 605.
Fibrillar collagen I matrix remodelling in idiopathic pulmonary fibrosis: Are lysyl oxidases responsible?
Authors: G. Tjin, T. Jegathees, A. Mahar, E.P.W. Kable, Janette Burgess
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: The development of fibrosis in Idiopathic Pulmonary Fibrosis (IPF) is a key feature and challenge in the treatment of the disease. The mechanisms of collagen I (COL1) reorganisation in the development of fibrosis, which may alter the stiffness of the tissue, are not well understood. Fibrillar COL1 has second harmonic generation (SHG) properties. SHG signals are coherent, propagating both in the forward (F) (primarily organized/mature collagen) and backward (B) (primarily disorganized/immature collagen) directions relative to the incident light. Collagen fibre maturity is governed by the degree of cross-linking and catalysed by enzymes from the Lysyl Oxidase family (LOX, LOXL1-4), which are implicated IPF pathology. The aim of this study was to investigate collagen I structural remodelling and the pathological role of Lysyl Oxidases in the development of fibrosis in IPF. Methods: Formalin fixed and paraffin embedded parenchymal tissues from non-diseased donors (n=8) and IPF explanted lungs (n=8) were analysed for SHG. F/B SHG signal ratio was used to determine the proportion of organized to disorganized collagen. Immunohistochemistry detected LOX and LOXL1 levels in tissues with single-blinded analysis to quantify colorimetric staining by computer-assisted image-analysis. Results: Increased F/B ratio was observed in IPF compared to non-diseased tissues (p=0.034) indicating increased COL1 fibre maturity in IPF. There was decreased LOX (p=0.009) and increased LOXL1 (p=0.031) expression in IPF. In lung tissues LOX negatively correlated with F/B ratio (p=0.0491, r2=0.249, n=16), while LOXL1 positively correlated with F/B ratio (p=0.003, r2=0.4898, n=16). Conclusion: Increased levels of COL1 fibre maturity in IPF could contribute to the increased stiffness of the tissue. LOXL1, but not LOX, may regulate the increased collagen fibre maturity in IPF tissues. These findings indicate there may be a specific role for LOX family members in the development of fibrosis in IPF.
Abstract 1809: Endothelin causes transactivation of the EGFR and Her-2/Neu in non-small cell lung cancer cells
Authors: Terry W. Moody, Irene Ramos Alvarez, Samuel Mantey, Robert T. Jensen
Journal: Cancer Research (2016)

Abstract Endothelin-1 (ET-1) is a 23 amino acid peptide which is present in many lung cancer cell lines (Ahmed et al., Am. J. Respir. Cell Mol. Biol. 2000; 22: 422). Expression of ET-1 or the ETA receptor is associated with poor prognosis of non-small cell lung cancer (NSCLC) patients (Boldrini et al., Eur. J. Cancer 2005; 41: 2828). ET-1 stimulates whereas the ETA antagonist ZD4054 inhibits the proliferation of cancer cells (Bagnato et al., Br. J. Pharmacol. 2011: 163; 220). Here the effects of ET-1 on the transactivation of the EGFR and Her-2/Neu were investigated in NSCLC cells. Twelve of 13 NSCLC cell lines tested had both ETA and ETB mRNA. Addition of ET-1 to adenocarcinoma cell line NCI-H838, which had both ETA and ETB mRNA, elevated cytosolic Ca2+, increased tyrosine phosphorylation of the ERK, EGFR and Her-2/Neu and increased colony number. The ability of ET-1 to increase cytosolic Ca2+, tyrosine phosphorylation of ERK, EGFR and Her-2/Neu and colony number was inhibited by ZD4054 or BQ123 (ETA antagonists). The transactivation of EGFR and Her-2/Neu by ET-1 was inhibited by lapatinib (EGFR and Her-2/Neu TKI), GM6001 (matrix metalloprotease inhibitor), PP2 (Src inhibitor) or N-acetylcysteine (anti-oxidant). ET-1 stimulated whereas lapatinib and ZD4054 inhibited the clonal growth of NSCLC cells. The results indicate that ET-1 may regulate the proliferation of NSCLC cells in an EGFR and Her-2/Neu-dependent manner. Citation Format: Terry W. Moody, Irene Ramos Alvarez, Samuel Mantey, Robert T. Jensen. Endothelin causes transactivation of the EGFR and Her-2/Neu in non-small cell lung cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1809.
Potential Therapy for Refractory Colon Cancer
Authors: Mitch Leslie
Journal: Cancer Discovery (2016)

The drug MM-1151 may overcome resistance to cetuximab and panitumumab caused by some mutations in the extracellular domain of EGFR. The drug slowed disease progression in a colorectal cancer cell line that carried some of the mutations and curbed growth of cells derived from a cetuximab-resistant patient tumor. In a phase I trial, tumors shrank or stabilized in patients who carried the mutations and received the drug.
A phase II study of erlotinib (E) and bevacizumab (B) in chemo naive patients (pts) with locally advanced or metastatic non small cell lung cancer (NSCLC)
Authors: V. van den Boogaart, A. de Langen, Hendricus Groen, J. Marcus, P. Kappert, W. Backes, B. Brans, O. Hoekstra, A. C. Dingemans, E. F. Smit
Journal: Journal of Clinical Oncology (2008)
Liquid biopsies will be routine NHS test for cancer “in under five years”
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

Liquid biopsies, which identify the genetic composition of cancer cells from a blood sample, are likely to be standard practice in the NHS within five years and possibly sooner, specialists have predicted.

The use of liquid biopsies will enable doctors to target treatments to a patient’s specific cancer and could save the NHS hundreds of millions of pounds by stopping treatments that do not work, said Johann de Bono, regius professor of cancer research at the Institute of Cancer Research, London, and consultant medical oncologist at the Royal Marsden NHS Foundation Trust.

Speaking at a briefing on liquid biopsies at the Science Media Centre in London on 4 August, de Bono said that the new technology is already …
Dasatinib Has Activity in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL/SLL), a Phase II Trial
Authors: Philip C. Amrein, Eyal Attar, Tak Takvorian, Ephraim Hochberg, Karen K. Ballen, Kathleen M. Leahy, Donna Neuberg, Jennifer R. Brown
Journal: Blood (2008)
Which CD8<sup>+</sup> T-cells in asthma? Attacking or defending?
Authors: Simonetta Baraldo, Graziella Turato, Manuel G. Cosio, Marina Saetta
Journal: European Respiratory Journal (2016)

There is considerable need to understand, and interest in understanding, the factors influencing the long-term prognosis of patients with asthma, especially considering the increase in life expectancy of this population. Thus, predicting the trajectories of lung function decline in ageing asthmatics has become an important task for current and future asthma management. CD8+ cells are associated with lung function decline in asthma but the subtype of CD8+ cells has to be better defined <http://ow.ly/iPQz300NuOT>
John Carter
Journal: BMJ (1889)

《约翰·卡特》并不是一部那么容易被搬上银幕的小说。一个世纪之前一位名叫埃德加·赖斯·巴勒斯的作家创造了约翰·卡特,生活在火星的地球人,面对荒凉又繁华的火星土地,面对与种族、与公主的分与合,约翰·卡特的人生绝对不简单。2012年恰逢《异星战场》的主角人物约翰·卡特诞辰1 OO周年,原著作家埃德加·赖斯·巴勒斯的另一部著作就是《泰山》,我很骄傲能为100周年这个里程碑作出一点贡献。导演安德鲁·斯坦顿说,《异星战场》是他首部真人电影,对于他本人来说这将是一次不小的尝试。在安德鲁·斯坦顿与马克·安德鲁斯、迈克尔·查邦一起创作剧本的时候,三个人发现了一个有趣的事情,他们都保留着小时候画过的约翰·卡特绘画作品以及《约翰·卡特》的周边产品,如今已经长大的三位编剧再次拿出这些满是回忆的东西,对《约翰·卡特》更加充满了喜爱。
Toxic Alcohol Calculations and Misinterpretation Of Laboratory Results—Reply
Authors: Michael Fralick, Kenneth Lam, Megan E. Himmel
Journal: JAMA Internal Medicine (2016)

In Reply We appreciate the interest and comments provided by Su and Hoffman, Lippi and Plebani, and Wu and Sivilotti in regards to our Teachable Moment “Hemodialysis in a Healthy Patient—A Case of an Erroneous Laboratory Result.”1
Abstract 4004: Development of a successful combination therapy for hepatocellular cancer by targeting Treg and PD-1
Authors: Dai Liu, Guangfu Li, Timothy Cooper, Eric Kimchi, Xiaoqiang Qi, Ningfei Li, Don Rockey, Todd Schell, Kevin Staveley-O’Carroll
Journal: Cancer Research (2016)

Abstract We have established a clinically relevant murine model to reveal tumor-induced immunotoerance in hepatocellular carcinoma (HCC). Critical factors are targeted to develop immune-based therapies for HCC control. Intrasplenic (ISPL) inoculation of oncogenic hepatocytes and intraperitoneal (IP) injection of carbon tetrachloride (CCl4) are combined to induce progressive HCCs in fibrotic livers of immunocompetent mice. We characterize the features of this model, examine tumor-antigen-specific (TAS) immunity during tumor initiation and progression, and identify the critical factors in tumor-induced immune tolerance. The established murine model recapitulates human HCC and reflects its typical features. TAS CD8+ T cells initially maintain a naive phenotype and function in early-stage tumor-bearing mice, then become profound exhaustion with the tumor progression to the advanced stage. The deep immunosuppression is associated with the significant upregulation of Programmed cell death protein 1(PD-1), Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the increase of Tregs. While the changes in Tregs and PD-1 are systemic, they are particularly pronounced in the tumor microenvironment. Sunitinib-mediated reduction of Treg together with antibody-mediated blockade of PD-1 synergistically suppress tumor growth and activate anti-tumor immunity. Our data provide evidence that oncogenic hepatocytes escape immune surveillance during tumor initiation via immune ignorance, while later-stage established HCCs evade immune destruction via tumor-induced immunotolerance. Synergy of sunitinib and anti-PD-1 Ab generates favorable effect on suppressing tumor growth and activating anti-tumor immunity. This combinational strategy has high translational potential in HCC treatment. Citation Format: Dai Liu, Guangfu Li, Timothy Cooper, Eric Kimchi, Xiaoqiang Qi, Ningfei Li, Don Rockey, Todd Schell, Kevin Staveley-O’Carroll. Development of a successful combination therapy for hepatocellular cancer by targeting Treg and PD-1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4004.