tbuckley/cabot-search huggingface dataset:
Abstract 5254: CARMIL3 promotes tumor progression in triple negative breast cancer: A possible novel biomarker
Authors: Jeeyeon Lee, Dong Won Baek, Soo Jung Lee, Jae-Hwan Jeong, In Hee Lee, Jin Hyang Jung, Ho Yong Park, Yee Soo Chae, Jieun Kang
Journal: Cancer Research (2019)

Abstract Purpose: CARMIL3 (LRRC16B, capping protein regulator and myosin 1 linker 3) was previously identified as a novel oncofetal-like gene. It influences cell proliferation, cell cycle control and transformation, possibly mediated by cyclin B1. This study aimed to investigate the function of CARMIL3 in triple negative breast cancer (TNBC) cells and tissues. Methods: CARMIL3 mRNA was measured using a qRT-PCR in breast cancer cells (MDA-MB-231, MCF7, SK-BR3 and T-47D) and tissues from 20 patients with TNBC. The effects of CARMIL3 on cell proliferation, migration, and invasion were determined using MTT, wound healing, and Matrigel Transwell assays. Results: Results showed that, the CARMIL3 mRNA expressions were significantly increased in breast cancer cell lines, especially in triple negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) when compared to normal breast epithelial cells (MCF10A). Downregulation of CARMIL3 inhibited the cell proliferation, migration and invasion of MDA-MB-231. Furthermore, high CARMIL3 mRNA expression was found in 20 TNBC specimens than normal controls (p&amp;lt;0.0001). Conclusions: In conclusion, CARMIL3 expression in TNBC affects cancer progression, which suggests that CARMIL3 can be a new biomarker for patients with TNBC. Citation Format: Jeeyeon Lee, Dong Won Baek, Soo Jung Lee, Jae-Hwan Jeong, In Hee Lee, Jin Hyang Jung, Ho Yong Park, Yee Soo Chae, Jieun Kang. CARMIL3 promotes tumor progression in triple negative breast cancer: A possible novel biomarker [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5254.
Prognosis of microsatellite instability and/or mismatch repair deficiency stage III colon cancer patients after disease recurrence following adjuvant treatment: results of an ACCENT pooled analysis of seven studies
Authors: J. Taieb, Q. Shi, L. Pederson, S. Alberts, N. Wolmark, E. Van Cutsem, A. de Gramont, R. Kerr, A. Grothey, S. Lonardi, T. Yoshino, G. Yothers, F.A. Sinicrope, A. Zaanan, T. André
Journal: Annals of Oncology (2019)
AB0036C IMMUNOPHENOTYPIC CHARACTERIZATION OF T-CELL IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH GOLIMUMAB
Authors: María-Mercedes Lopez-Mayorga, Rosa-Elda Barbosa-Cobos, Mario Adán Moreno-Eutimio, Lizbeth Teresa Becerril Mendoza, Pedro Rodríguez Henríquez, Gustavo Lugo, Lucía-Verónica Maya-Piña, Olivia Hernández-Jaimes, José Moreno
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Golimumab is a human anti-TNF monoclonal antibody that has shown efficacy in RA. In the RA pathophysiology, the elevation of TNF modulates the cellular immune response, which leads to a sustained activation of T-cell response; however, it is unknown whether anti-TNF interferes with the immunophenotype of T-cell. <h3>Objectives:</h3> To evaluate activation (CD25, CD69) and exhausted (PD-1, TIM-3, LAG-3, CTLA-4) markers of T-cells in RA patients treated with Golimumab. <h3>Methods:</h3> We included 14 patients with RA diagnosis (Criteria ACR/EULAR 2010), with moderate to severe activity; 11 non-responders to synthetic DMARDs (NR-DMARDs) and 3 responders to synthetic DMARDs with pharmacological toxicity (R-DMARDs). All patients were treated with Golimumab during 24 weeks. The questionnaire SF-36, DAS28-CRP, power Doppler signal and expression of CD25, CD69, PD-1, TIM-3, LAG-3 and CTLA-4, in T-cell were evaluated at 0 and 24 weeks. <h3>Results:</h3> Clinical variables evaluated in patients with Rheumatoid Arthritis are shown in tables 1 and 2. The frequency of LAG-3+ on CD4+ T-cells increased after 24 weeks of treatment with Golimumab (p = 0.013) (figure 1). The expression of LAG-3 in CD4+ T-cells (r = -0.586, p = 0.028) (Figure 2) and CD8+ T-cells (r = -0.617, p = 0.019) (Figure 3) inversely correlated with DAS28-CRP after treatment. At the beginning of treatment NR-DMARDs patients showed higher expression of CD25 in CD8+ T-cells and lower expression of TIM-3 in CD4+ and CD8+ T-cells with respect to R-DMARDs. After 24 weeks of treatment, a lower frequency of CD69+ and LAG-3+ T-cells was found and increased of CD25+ T-cells compared to R-DMARDs. <h3>Conclusion:</h3> Golimumab treatment increased the expression of LAG-3 in T-cells, suggesting a negative regulator of antigen presentation of T-cells. <h3>References</h3> [1] Tahir Z, Kavanaugh A. The role of golimumab in inflammatory arthritis. A review of the evidence. Ther Adv Musculoskel Dis2018;9:181–194. [2] Cuda C, Pope R, Perlman H. The inflammatory role of phagocyte apoptotic pathways in rheumatic diseases. Nat rev Rheumatol2016;12: 543-555. [3] Wherry E, Kurachi M. Molecular and celular insights into T cell exhaustion. Nat rev Inmunol 2015;15: 486-496. [4] Burmester G, Feist E, Dörner T. Emerging cell and cytokine targets in rheumatoid arthritis. Nat rev Inmunol2013;15:1-10. [5] McKinney E, Lee J, Jayne D, Lyons P. T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection. Nat rev Inmunol2015;523: 612-616. <h3>Disclosure of Interests:</h3> None declared
Abstract 5920: Lecithin Cholesterol Acyltransferase Promotes Reverse Cholesterol Transport and Attenuates Atherosclerosis Progression in New Zealand White Rabbits
Authors: Mingyue Zhou, Janet Sawyer, Kathryn Kelley, Preston Fordstrom, Joyce Chan, George Tonn, Tim Carlson, Marc Retter, Dave Meininger, Janet Cheng, Andrew Gates, Anne Woodward, John Delaney, Richard Zhang, Jay Tang, Qiang Liu, Ping Cao, Jayraz Luchoomun, Jason Voogt, Scott Turner, Bei Shan, Tom Boone, Lawrence Rudel, Margrit Schwarz
Journal: Circulation (2009)

Background: Low plasma levels of high density lipoprotein cholesterol (HDL-C) are associated with an increased risk of cardiovascular disease (CVD), and there is an unmet need for novel therapies t...
Endoscopic reversal of vertical banded gastroplasty: a novel use of electroincision
Authors: Jessica X. Yu, Arpan Patel, Ryan Law
Journal: Endoscopy (2019)

Vertical banded gastroplasty (VBG) was introduced in 1982 as a restrictive form of weight loss surgery through the creation of a pouch using a vertical staple line and outlet restriction with a silastic band [1]. However, the popularity of VBG has waned due to high adverse event rates and the need for surgical revision [2]. We present the case of an endoscopic reversal of a VBG using electroincision ([Video 1]).
Surgical and combined treatment for patients with cholangiocarcinoma: the experience of FSBI
Authors: A. Polyakov, Y. Patutko, I. Pokataev, D. Podluzhnyi, I. Sagaidak, I. Bazin, Y. Chikhareva, A. Syskova, I. Bazina, A. Yastrebova, M. Magomedov
Journal: Annals of Oncology (2019)
Abstract 2607: BPTF role in melanoma progression and BRAF resistance therapy
Authors: Altaf A. Dar, Shahana Majid, David de Semir, Vladimir Bezrookove, Mehdi Nosrati, Mohammed Kashani-Sabet
Journal: Cancer Research (2019)

Abstract Bromodomain PHD finger transcription factor (BPTF) plays an important role in chromatin remodeling, but its functional role in tumor progression is incompletely understood. Here we reveal new pro-oncogenic roles for BPTF in promoting tumor cell proliferation and resistance to targeted therapies. shRNA-mediated BPTF silencing suppressed the proliferative capacity (by 65.5%) and metastatic potential (by 66.4%) of melanoma cells. Elevated BPTF mean copy number greater than 3 was observed in 28 of 77 (36.4%) melanomas. BPTF overexpression predicted poor survival in a cohort of 311 melanoma patients (distant metastasis-free survival, p=0.03, and disease-specific survival p=0.008), and promoted resistance to BRAF inhibitors in melanoma cell lines. Metastatic melanoma tumors progressing on BRAF inhibitors contained low BPTF-expressing, apoptotic tumor cell sub-clones, indicating the continued presence of drug-responsive sub-clones within tumors demonstrating overall resistance to anti-BRAF agents. These studies demonstrate multiple pro-tumorigenic functions for BPTF, and identify it as a novel target for anti-cancer therapy. They also suggest the combination of BPTF targeting with BRAF inhibitors as a novel therapeutic strategy for melanomas with mutant BRAF. Citation Format: Altaf A. Dar, Shahana Majid, David de Semir, Vladimir Bezrookove, Mehdi Nosrati, Mohammed Kashani-Sabet. BPTF role in melanoma progression and BRAF resistance therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2607.
Knowledge and global health: reducing the burden of non-communicable diseases using physical activity
Authors: Steve Aspinall, Allan Munro
Journal: British Journal of Sports Medicine (2019)

In this BASRaT guided issue of BJSM, we look at how we can support healthy lifestyles for our patients, athletes and also to improve public health (figure 1). In its global action plan on physical activity (PA; 2018–2030) the WHO sets out four strategic objectives for a healthier world; to create active societies, active people, active environments and active systems. Achieving these goals will help prevent and treat non-communicable diseases (NCDs), including heart disease, stroke, diabetes and breast and colon cancer.1 



Figure 1 
Supporting healthy lifestyles - what can we do to make a difference?



Increasing PA improves the key disease risk factors hypertension and obesity as well as having a positive effect on mental health, delaying the onset of dementia and improving both quality of life and well-being.1 By helping our patients become more active Sports Rehabilitators can play a key role in reducing the social and economic burden of NCDs across the world.

We clinicians know we want people to be more active, we know the potential rewards for both individuals and society more generally but how do we achieve these goals? Knowledge informs clinical practice and we need to apply that to find opportunities for adding PA to peoples’ lives. This is supported in the UK by …
Pompholyx vesicles contain small clusters of cells with high levels of hyaluronate resembling the pustulovesicles of palmoplantar pustulosis
Authors: M. Murakami, J. Muto, K. Masuda‐Kuroki, T. Tsuda, H. Mori, R. Utsunomiya, K. Shiraishi, K. Sayama
Journal: British Journal of Dermatology (2019)
From leadership to biodiversity: the good of small things
Authors: Kamran Abbasi
Journal: BMJ (2019)

Small things matter. The biologist E O Wilson was first a world expert in myrmecology, the study of ants, before his appreciation of our planet’s evolutionary progress and what the future might hold turned him into the “father of biodiversity.” In The God of Small Things by Arundhati Roy we learn the importance of focusing on the smaller matters of the here and now when our bigger ambitions seem too distant to touch.

You might argue that we shouldn’t sweat the small stuff, as the psychotherapist Richard Carlson put it, but can a leader, whether in biodiversity, environmental activism, or healthcare, afford to keep …
Self-management of Epilepsy
Authors: Matthew W. Luedke, Dan V. Blalock, Karen M. Goldstein, Andrzej S. Kosinski, Saurabh R. Sinha, Connor Drake, Jeffrey D. Lewis, Aatif M. Husain, Allison A. Lewinski, Abigail Shapiro, Jennifer M. Gierisch, Tung T. Tran, Adelaide M. Gordon, Megan G. Van Noord, Hayden B. Bosworth, John W. Williams
Journal: Annals of Internal Medicine (2019)

Background: Although self-management is recommended for persons with epilepsy, its optimal strategies and effects are uncertain. Purpose: To evaluate the components and efficacy of self-management interventions in the treatment of epilepsy in community-dwelling persons. Data Sources: English-language searches of MEDLINE, Cochrane Central Register of Controlled Trials, PsycINFO, and CINAHL in April 2018; the MEDLINE search was updated in March 2019. Study Selection: Randomized and nonrandomized comparative studies of self-management interventions for adults with epilepsy. Data Extraction: An investigator assessed study characteristics; intervention details, including 6 components of self-management; and outcomes, which were verified by a second reviewer. Risk of bias (ROB) was assessed independently by 2 investigators. Data Synthesis: 13 randomized and 2 nonrandomized studies (2514 patients) evaluated self-management interventions. Interventions were delivered primarily in group settings, used a median of 4 components, and followed 2 general strategies: 1 based on education and the other on psychosocial therapy. Education-based approaches improved self-management behaviors (standardized mean difference, 0.52 [95% CI, 0.0 to 1.04]), and psychosocial therapy–based approaches improved quality of life (mean difference, 6.64 [CI, 2.51 to 10.77]). Overall, self-management interventions did not reduce seizure rates, but 1 educational intervention decreased a composite of seizures, emergency department visits, and hospitalizations. Limitation: High ROB in most studies, incomplete intervention descriptions, and studies limited to English-language publications. Conclusion: There is limited evidence that self-management strategies modestly improve some patient outcomes that are important to persons with epilepsy. Overall, self-management research in epilepsy is limited by the range of interventions tested, the small number of studies using self-monitoring technology, and uncertainty about components and strategies associated with benefit. Primary Funding Source: U.S. Department of Veterans Affairs. (PROSPERO: CRD42018098604)
Abstract 121: S100A9 inhibitor Tasquinimod: A novel strategy to inhibit small cell lung cancer progression and metastasis
Authors: Salha E. Sassi, Dinesh Ahirwar, Ramesh K. Ganju
Journal: Cancer Research (2019)

Abstract Small cell lung cancer (SCLC) treatment is a major clinical challenge at present as it is highly refractory to available drugs. The MDSCs/macrophages are known to help SCLC develop resistant to available therapies. S100A9 (Migration inhibitory factor-related protein 14 (MRP14) is an EF-hand calcium-binding protein that has been involved in cell migration, invasion, proliferation, and tumor metastasis in various type of cancers, however not much is known about its role in SCLC. In this study, we found that S100A9 protein is highly up-regulated in various types of pulmonary neuroendocrine carcinomas (NEC) patient tissues compared to normal using tissue microarrays. We also observed that SCLC patients with higher S100A9 expression have significantly increased numbers of macrophage in the stroma. We have also shown that pre-treatment of the cells with S100A9 inhibitor (Tasquinimod) suppressed in-vitro cell migration, invasion, and colony formation. In addition, we analyzed the efficacy of S100A9 inhibitor against SCLC using in vivo mouse models. S100A9 inhibitor significantly reduces tumor growth and metastasis in SCLC in xenograft mouse models. We further observed that S100A9 inhibitor suppressed myeloid-derived suppressor cells (MDSC) populations and TAMs of the M2-polarized phenotype in SCLC. Moreover, we found myeloid cells sequestered from tumors of treated mice expressed were MI type as they showed higher levels of inducible nitric oxide synthase (iNos), and lower levels of arginase-1. Molecular analysis revealed that Tasquinimod decreases expression of IL6, IL10, and TGF-β1 in the cancer cells which helps inhibit macrophage activation to TAMs. Reduced proliferation and vascularization were observed in the tumors obtained from animals treated with S100A9 inhibitor. We also observed S100A9 inhibitor suppressed osteolytic bone formation in ex-vivo resorption assay. Overall, our studies, for the first time, show that Tasquinimod that targets S100A9 signaling could be used as a novel therapeutic strategy against SCLC. Citation Format: Salha E. Sassi, Dinesh Ahirwar, Ramesh K. Ganju. S100A9 inhibitor Tasquinimod: A novel strategy to inhibit small cell lung cancer progression and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 121.
Abstract 4810: Olive oil-derived (-)-oleocanthal for prevention of breast cancer recurrence
Authors: Abu Bakar Siddique, Nehad M. Ayoub, Khalid A. El Sayed
Journal: Cancer Research (2019)

Abstract Despite progress in BC therapy and improved survival rates, several breast cancer (BC) patients have poor recurrence-free rates. More than three million BC survivors are currently at the risk of disease recurrence without feasible preventive options. Surgical excision of early-stage confined breast tumors commonly used to minimize subsequent metastasis. Neoadjuvant and adjuvant therapeutic agents usually cannot prevent BC recurrence. There is a dire need to discover novel recurrence and metastasis inhibitory entities because clinical trials on early-stage cancer patients survival and metastases/recurrence reduction endpoint is not financially feasible and need large patients number. Mediterranean populations have less colon and breast cancers incidence due to their dietary consumption of significant amounts of phenolics-rich extra-virgin olive oil (EVOO). (-)-Oleocanthal (OC) is the most bioactive EVOO phenolic with diverse activities and exceptional in vivo potency. Validated molecular targets of OC in BC include the inhibition of the activation of the RTKs c-Met and HER2 and modulation of estrogen receptors (ER). Met/HER2/ER amplification is implicated in activation of quiescent breast tumor cells, repopulation, subsequent recurrence and relapse. This study reports the potent ability of four-weeks oral 10 mg/kg OC treatments to inhibit more than 90% of local and regional triple negative and hormone-dependent breast tumors recurrence after the surgical excision of orthotopically xenografted primary breast tumors. Oral OC treatments also potently inhibited recurrence after surgical excision of breast tumors subjected to neoadjuvant therapies with either lapatinib (50 mg/kg, 5X/week, 4 weeks) or paclitaxel (4.5 mg/kg, ip, 3X/week for 6 weeks) in athymic orthotopic nude mice models. This was associated with significant reductions of p-c-Met and p-HER2 levels in treated animal tumors by Western blotting. OC-treated mice sera completely lacked the BC recurrence marker CA 15-3, unlike vehicle treated controls which showed significantly high CA 15-3 levels. OC treatment did not show any observable toxicity and did not affect animals body weight over the experiment course. OC is a novel breast cancer recurrence inhibitory dietary supplement lead with excellent clinical applications potential. Note: This abstract was not presented at the meeting. Citation Format: Abu Bakar Siddique, Nehad M. Ayoub, Khalid A. El Sayed. Olive oil-derived (-)-oleocanthal for prevention of breast cancer recurrence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4810.
Expression of CCL5 (RANTES) and its receptors in prostate cancer
Authors: Gayle G. Vaday, Donna M. Peehl, Pournima A. Kadam, Diana M. Lawrence
Journal: Cancer Research (2005)

4696  Inflammation has long been considered a contributing factor in the development and advancement of cancer. Expression of the prototypic inflammatory chemokine CCL5 (RANTES) by tumor cells is thought to correlate with the progression of several cancers, through the recruitment of inflammatory leukocytes. Furthermore, CCL5 was shown to induce breast cancer cell migration, mediated by the receptor CCR5. A CCR5 antagonist was also demonstrated to inhibit experimental breast tumor growth. Recently, CCL5 and CCR5 mRNA expression was reported in prostate cancer (PCa) tissues. In this study, we characterized CCL5 and CCR5 expression in cultures of PCa cells and explored possible functions of CCL5 in PCa progression. CCL5 mRNA and protein expression were found in human PCa cell lines (PC-3; DU-145; LNCaP) and primary prostate adenocarcioma cells by quantitative RT-PCR and ELISA. CCL5 was detected in human PCa tissues by immunohistochemical staining. CCR5 expression was demonstrated on the cell-surface of PCa cells by flow cytometry, as well as in large intracellular pools within the cells. To determine whether PCa cell-derived CCL5 may affect inflammatory cell infiltration, monocyte chemotaxis assays were performed. Conditioned media from PCa cells induced THP-1 monocyte chemotaxis, which was inhibited by anti-CCL5 antibodies. We further studied whether CCL5 directly affects PCa cells. We found that incubation with CCL5 (10-100 ng/ml) induced PCa cell proliferation, and that the CCR5 antagonist TAK-779 inhibited CCL5-induced proliferation. CCL5 was also found to stimulate PCa cell invasion through basement membrane gels, and TAK-779 inhibited CCL5-induced cell invasion. In light of growing evidence that inflammation influences the pathogenesis of PCa, these results suggest that chemokines, such as CCL5, expressed by prostate cells may affect the degree of local inflammatory infiltrates, as well as act directly on the growth and survival of PCa cells. Chemokine receptor antagonists may thus block both paracrine and autocrine mechanisms of PCa progression.
Safety and Efficacy of Daratumumab Monotherapy in Patients with Heavily Pretreated Relapsed and Refractory Multiple Myeloma: Final Results from GEN501 and Sirius
Authors: Saad Z Usmani, Hareth Nahi, Brendan M Weiss, Nizar J. Bahlis, Andrew Belch, Henk M Lokhorst, Peter M. Voorhees, Paul G Richardson, Clarissa Uhlar, Jianping Wang, Ming Qi, Sagar Lonial
Journal: Blood (2017)
Insight into the management of actinic keratosis
Authors: E.C. Noels, M. Lugtenberg, S. Egmond, S.M. Droger, P.A.J. Buis, T. Nijsten, M. Wakkee
Journal: British Journal of Dermatology (2019)

Actinic keratoses (AK) are rough skin lesions (patches) caused by long‐term sun exposure in light skinned individuals, affecting 24‐60% of people above the age of 50. The current management of AK patients (meaning how they are diagnosed and treated and how long they are ‘followed up’ for) seems to vary within and between primary care (e.g. GPs) and secondary care (e.g. hospital dermatology departments). This Dutch study aimed to provide insight into underlying motives of current AK management. A study was conducted consisting of interviews with 22 general practitioners (GPs) and 18 dermatologists. GPs varied in their methods for diagnosing AK and in determining treatment and follow‐up schedules, due to a lack of knowledge and experience and low perceived value of AK care. Dermatologists indicated that they strived to provide AK care according to official guidelines, although patient preferences and other patient‐related factors influence treatment choices and often lead to extensive follow‐up regimens. For AK care to become more standardized and uniform in Dutch primary care, implementation of guidelines and continuing education are needed, to address the commonly reported barriers of lack of value, experience and knowledge among GPs. To help prevent extensive follow‐up in secondary care (and therefore to ensure efficient use of care), shared decision‐making tools along with adequate patient information may be useful to help dermatologists’ management of patient preferences.