tbuckley/cabot-search huggingface dataset:
P5-13-23: Individualized Treatment Strategies for HER2−Negative Breast Cancer Subtypes.
Authors: T Ishikawa, D Shimizu, A Yamada, T Sasaki, S Morita, M Tanabe, K Kawachi, A Nozawa, T Chishima, M Kimura, Y Ichikawa, I Endo
Journal: Cancer Research (2011)

Abstract Background Human epidermal growth factor receptor (HER2)-negative breast cancers are more heterogeneous than HER2−positive cancers, and tailored treatment is therefore required for luminal A and triple-negative breast cancer subtypes (LABC and TNBC). We therefore examined predictive factors for the efficacy of standard chemotherapy in LABC and TNBC subtypes. Methods A total of 109 LABC and 61 TNBC patients were treated with standard neoadjuvant chemotherapy (NAC) consisting of an anthracycline and/or taxane. The pathological treatment response and prognosis were examined for each subtype. Expression levels of the following factors were examined in association with quasi-pathological complete response (QpCR): estrogen- and progesterone-receptor (ER and PgR) status, HER2, nuclear grade, MIB-1, p53, topoisomerase IIα (topoIIα), cytokeratin (CK) 5/6 and epidermal growth factor (EGFR). Results QpCR rates in LABC and TNBC were 9.1% (10/109) and 54.1% (33/61), respectively. In LABC, the expression of PgR tended to be inversely associated with pathological response (p=0.087), while in TNBC, increased expression of topoIIa (p=0.006) and MIB-1 (p=0.018) were identified as predictors of QpCR. TopoIIα expression was also significantly associated with pathological response in multivariate analysis (p=0.014). The QpCR rate was higher in TNBC lacking CK5/6 and/or EGFR expression, defined as non-basal subtype (p=0.053). Conclusions Low expression of PgR may be a possible predictor of the efficacy of chemotherapy in LABC, while a high level of proliferative activity, indicated by topoIIa and MIB-1, is associated with chemosensitivity in TNBC. Further subclassification into basaland non basal-subtypes may also be helpful for the development of individualized treatments. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-23.
Abstract 4948: Pirfenidone as a potential therapeutic treatment for CAFs and cancer cells in NSCLC.
Authors: Melanie Mediavilla-Varela, Kimberly Luddy, David Noyes, Kingsley Boateng, Scott Antonia
Journal: Cancer Research (2013)

Abstract Lung cancer is the leading cause of cancer death in the United States. Due to limited efficacy of current conventional chemotherapy, the majority of patients face poor prognosis and eventually succumb the disease. Until recently, the main focus in cancer research has been targeting the neoplastic cell. However, the importance of the tumor microenvironment, including cancer associated fibroblasts (CAFs), in cancer progression is now clear and targeting both, the neoplastic cell as well as the CAF, is being recognized as an important therapeutic approach. We have recently discovered that pirfenidone might be the drug to target these cells. Pirfenidone is a small molecule that has been shown to decrease fibrosis in a variety of fibrotic diseases. The exact mechanism responsible for its anti-fibrotic effects remains to be elucidated. Our hypothesis is that pirfenidone (by targeting the CAFs) in combination with standard chemotherapy (by targeting the cancer cells) will act synergistically and proffer a more potent therapeutic strategy for non-small cell lung cancer (NSCLC). Our studies show that in the presence of pirfenidone NSCLC associated CAF viability decreases in vitro. Furthermore, pirfenidone was able to induce apoptotic cell death as well as cell cycle arrest in NSCLC associated CAFs. In addition, we were able to observe that CAFs treated with pirfenidone decreased active TGFβ when compared to the control. Moreover, in a spheroid model, pirfenidone was able to affect the crosstalk between the cancer cells and CAFs leading to increased apoptosis and decreased viability. Currently, pirfenidone is being used in Phase II and III clinical trials for idiopathic pulmonary fibrosis. Our lab is the first one to recognize the potential of pirfenidone as a potential treatment of NSCLC. Citation Format: Melanie Mediavilla-Varela, Kimberly Luddy, David Noyes, Kingsley Boateng, Scott Antonia. Pirfenidone as a potential therapeutic treatment for CAFs and cancer cells in NSCLC. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4948. doi:10.1158/1538-7445.AM2013-4948
A Heavy Heart
Authors: Amy Leigh Miller, Rodney H. Falk, Bruce D. Levy, Joseph Loscalzo
Journal: New England Journal of Medicine (2010)

A 73-year-old man presented with a history of progressive, symmetric edema that began in the lower extremities and extended to involve his thighs, scrotum, and arms. He had dyspnea on exertion, orthopnea, and paroxysmal nocturnal dyspnea, as well as chest pressure on mild exertion.
Soft-Tissue Uptake of Colonic Metastases
Authors: S. F. HAIN, R. A. COOPER, R. S. ARONEY, S. KING, P. J. ROACH
Journal: Clinical Nuclear Medicine (1999)

Tc-99m MDP uptake into extraosseous malignant lesions with metastases to soft tissue has been well described. Tc-99m MDP uptake has been reported in primary lesions and usually in single metastatic sites including the regional lymph nodes, the abdomen, and especially the liver. In metastatic adenocarcinoma, previous studies showing extraosseous uptake have revealed histopathologically that calcification or ossification had occurred in the soft tissue. The authors report an unusual case of soft-tissue metastases in colonic adenocarcinoma that were detected on routine bone scintigraphy. The histopathologic findings did not reveal calcification, ossification, or necrosis.
Fines for breaching NHS performance targets are “counterproductive”
Authors: Gareth Iacobucci
Journal: BMJ (2016)

Around £600m (€760m; $860m) of funding will be withheld from NHS hospitals and other healthcare providers this financial year (2015-16) because of fines imposed for breaching key performance targets, a new analysis has shown.

NHS Providers, the body representing NHS hospitals that conducted the analysis for the Guardian newspaper,1 said that the fines imposed by NHS clinical commissioning groups were counterproductive, risking driving the trusts into further deficit and delaying patient care.

The group said that the penalties for breaching waiting time and treatment targets had increased the NHS providers’ financial risk at a time of …
IMPACT OF PRIOR CEREBROVASCULAR EVENTS ON ISCHEMIC AND BLEEDING OUTCOMES WITH CANGRELOR IN PERCUTANEOUS CORONARY INTERVENTION
Authors: Neal Narain Sawlani, Robert Harrington, Gregg Stone, Philippe Steg, C. Michael Gibson, Christian Hamm, Matthew Price, Jayne Prats, Efthymios Deliargyris, Kenneth Mahaffey, Harvey White, Deepak L. Bhatt
Journal: Journal of the American College of Cardiology (2016)
Association between Tumor Necrosis Factor-α and Disease Progression in Patients with Multiple Sclerosis
Authors: Mohammad K. Sharief, Romain Hentges
Journal: New England Journal of Medicine (1991)

Cachectin, or tumor necrosis factor-alpha (TNF-alpha), is a principal mediator of the inflammatory response and may be important in the pathogenesis and progression of multiple sclerosis, an inflammatory disease of the central nervous system.In a 24-month prospective study, we used a sensitive enzyme-linked immunosorbent assay to determine levels of TNF-alpha in cerebrospinal fluid and serum in 32 patients with chronic progressive multiple sclerosis and in 20 with stable multiple sclerosis and 85 with other neurologic diseases. An attempt was made to relate TNF-alpha levels with the degree of disability of the patients with multiple sclerosis and with their neurologic deterioration during the 24 months of observation.High levels of TNF-alpha were found in the cerebrospinal fluid of 53 percent of the patients with chronic progressive multiple sclerosis and in none of those with stable multiple sclerosis (P less than 0.001). TNF-alpha was detected in the cerebrospinal fluid of 7 percent of the controls (P less than 0.01) with other neurologic disease. In patients with chronic progressive multiple sclerosis, mean TNF-alpha levels were significantly higher in the cerebrospinal fluid than in corresponding serum samples (52.41 vs. 11.88 U per milliliter; range, 2 to 178 vs. 2 to 39; P less than 0.001). In these patients, cerebrospinal fluid levels of TNF-alpha correlated with the degree of disability (r = 0.834, P less than 0.001) and the rate of neurologic deterioration (r = 0.741, P less than 0.001) before the start of the study. Cerebrospinal fluid levels also correlated with the increase in neurologic disability after 24 months of observation (r = 0.873, P less than 0.001).These data provide evidence of intrathecal synthesis of TNF-alpha in multiple sclerosis and suggest that the level of TNF-alpha in cerebrospinal fluid correlates with the severity and progression of the disease. Our results suggest that TNF-alpha may reflect histologic disease activity in multiple sclerosis and could be used to monitor outcomes or responses to therapy.
Abstract 3651: Phosphatidylserine-targeting antibody induces differentiation of myeloid-derived suppressor cells into M1-like macrophages
Authors: Xianming Huang, Dan Ye, Philip E. Thorpe
Journal: Cancer Research (2011)

Abstract Introduction: The phosphatidylserine (PS)-targeting antibody, bavituximab, is currently in Phase IIb clinical trials in patients with lung cancer. Bavituximab, and its murine counterpart, 2aG4, induce the attack of monocytes and macrophages on PS-expressing tumor vascular endothelium and tumor cells and inhibit the immunosuppressive effects of PS in the tumor microenvironment. Myeloid-derived suppressor cells (MDSC) are one of the major cells responsible for the immunosuppressed state in tumors. In this study, we tested the influence of 2aG4 on the differentiation of MDSC into M1-like tumor associated macrophages (TAMs). Methods: MDSC were isolated from 4T1 tumor bearing mice with anti-Gr1-coated magnetic beads. The purified MDSC were then cultured for 5 days in the presence of 2aG4 or control C44 antibody. For in vivo studies, PC3 tumor-bearing mice were treated with 2aG4 for 30 days and MDSC and TAMs in tumors and spleens were analyzed by FACS and immunohistochemistry. Results: 2aG4 treatment of purified MDSC switched their cytokine production from an immunosuppressive IL-10-dominated response to a pro-inflammatory IL-12- and TNFα -dominated response. The percentage of Gr1+ cells decreased to 8% in the 2aG4-treated cultures (P&amp;lt;0.0001) but only to 50 – 57% in the PBS and C44-treated cultures. Treatment with 2aG4 induced the differentiation of MDSC into M1-like macrophages that expressed lower CD206 and produced more NO than control cultures. Treatment of mice bearing PC3 prostate tumors with 2aG4 decreased the percentage of MDSC from 7% to 4% (P&amp;lt;0.001) in the tumors and from 28% to 20% (P&amp;lt;0.001) in the spleens. The antibody treatment also increased the ratio of M1 to M2 TAMs in PC3 tumors from 0.7% to 1.4% (P&amp;lt;0.001). Conclusion: Taken together, our results suggest that 2aG4 causes the differentiation of MDSCs into macrophages having an M1-like phenotype. 2aG4 treatment decreased IL-10 production and increased IL-12 and TNFα-production. These results suggest that 2aG4 treatment reactivates innate immunity in tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3651. doi:10.1158/1538-7445.AM2011-3651
FROZEN ELEPHANT TRUNK FOR TYPE A AORTIC DISSECTION: INTERACTIONS OF TRANSFER DISTANCE, ACUITY AND MORTALITY
Authors: Wei-Guo Ma, Long-Fei Wang, Sven Peterss, Wei Zhang, Jun Zheng, Xu-Dong Pan, Yong-Min Liu, Jun-Ming Zhu, John Elefteriades, Li-Zhong Sun
Journal: Journal of the American College of Cardiology (2016)
IMPROVEMENT OF LEFT VENTRICULAR DIASTOLIC FUNCTION 30 DAYS AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT FOR SEVERE AORTIC STENOSIS
Authors: Julie Friedman, Prashant Atri, John Blair, Kent Brummel, Issam Mikati, S. Chris Malaisrie, Ranya Sweis, Charles Davidson, James Flaherty
Journal: Journal of the American College of Cardiology (2016)
COMBINED ASSESSMENT OF RIGHT VENTRICULAR FUNCTION AND MID-TERM REVERSE REMODELING IN RIGHT-SIDED HEART ENHANCES PROGNOSTIC CAPABILITY FOR PULMONARY HYPERTENSION PATIENT OUTCOME AFTER MEDICAL TREATMENT
Authors: Hiroyuki Sano, Hidekazu Tanaka, Yoshiki Motoji, Yuko Fukuda, kumiko Dokuni, Yutaka Hatani, Keiko Hatazawa, Hiroki Matsuzoe, Hiromi Toki, Hiroyuki Shimoura, Junichi Ooka, Takuma Sawa, Yasuhide Mochizuki, Keiko Ryo, Kensuke Matsumoto, Noriaki Emoto, Ken-ichi Hirata
Journal: Journal of the American College of Cardiology (2015)
Abstract 4303: The Jackson Laboratory Repository: resource for mouse strains modeling cancer
Authors: Deborah M. Boswell, Leah Rae Donahue, Cathleen M. Lutz, Stephen F. Rockwood, Michael Sasner
Journal: Cancer Research (2011)

Abstract The Jackson Laboratory Repository is an established resource for the importation, cryopreservation, development, and distribution of mouse strains vital to biomedical research. More than 500 new strains are added annually to the approximately 5,000 strains and stocks of mice currently held in the Repository collection. Newly acquired or developed strains include a model of malignant melanoma and metastasis; a xenotransplant model that provides continuous circulation of human growth factors; a targeted mutation strain for studying myeloproliferative diseases such as chronic myelomonocytic leukemia and Chronic Familial Myelocytic Leukemia-Like Syndrome; and a knock-in strain that mimics the t(9;11)(p22;q23) translocation identified in acute myeloid leukemia. Also under development are a transgenic/targeted mutation strain with increased mammary gland tumor incidence and three targeted mutation strains with increased sensitivity to carcinogens or radiation. The Repository's inducible and conditional mutation mouse strains allow researchers to generate temporal and/or tissue-specific tools for modeling human cancer. New additions to the Repository collection include strains with Cre recombinase expression specific to the colon and rectum, as well as a transgenic strain that can be used as part of a bitransgenic system utilizing the tetracycline-inducible expression of a gene of interest in blood vessel endothelial cells. For non-invasive in-vivo imaging studies, the Repository distributes a xenograft/transplant host with widespread expression of firefly luciferase and enhanced green fluorescence protein. The Repository maintains a searchable on-line resource (www.jax.org) for each strain. Researchers can submit their strains to be considered for inclusion in the Repository by using the on-line form available at The Jackson Laboratory website: http://www.jax.org/grc/index.html. The Jackson Laboratory Repository is supported by the NCRR, The Howard Hughes Medical Institute, The Ellison Medical Foundation and donations from private charitable foundations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4303. doi:10.1158/1538-7445.AM2011-4303
Men more likely to die from malignant melanoma than women
Authors: A. Cole
Journal: BMJ (2013)

Many more men than women are dying from malignant melanoma, according to the latest figures from Cancer Research UK, despite the fact that similar numbers are being diagnosed each year.

The latest data1 show that 3.4 men (95% confidence interval 3.2 to 3.5) per 100 000 died in 2011, compared with two women (1.8 to 2.1) per 100 000, meaning that the death rate in men was 70% higher. Yet the incidence of melanoma is similar, with 17.2 …
The Use and Abuse of Chemotherapeutic and Antibiotic Agents
Authors: Perrin H. Long
Journal: New England Journal of Medicine (1947)

TEN years have passed since the sulfonamides were introduced into general therapy in this country. Notable reductions in the case mortality rates of streptococcal, meningococcal and pneumococcal infections have followed the use of these drugs. The course of gonococcal, staphylococcal and other stubborn bacterial infections has been radically altered by therapy with the sulfonamides. One can say without exaggeration that the success, as well as the failures, of the sulfonamides stimulated research that led to the development of penicillin and the discovery of streptomycin. Today the physician has a choice of chemotherapeutic and antibiotic agents with which to combat infectious . . .
676 INCREASING PREVALENCE OF ENTEROCOCCAL PERITONITIS IN CIRRHOSIS: A SINGLE-CENTER RETROSPECTIVE ANALYSIS OF ASCITIC FLUID CULTURES 1997-2011
Authors: P.A. Reuken, M. Baier, W. Pfister, M.W. Pletz, A. Stallmach, T. Bruns
Journal: Journal of Hepatology (2012)
THU0250 Treat to Target in Early Rheumatoid Arthritis Clinic (EAC): Low Radiological Progression and Good Functional Outcomes on Conventional Disease Modifying Drugs (DMARDS)
Authors: O. Semenova, H. Thompson, S. Kallankara, O. Ogunbambi, Y. patel, E. Baguley
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> EAC was established in 2010, where we used protocol-driven rapidly escalating treatment with combination of conventional DMARDs. High remission rates (DAS28), achieved after 1 year of this treatment have been previously reported [1], but progression of the disease has not been analysed. <h3>Objectives</h3> To analyse the results of radiological, functional and employment outcomes after 1 year of treatment in EAC. <h3>Methods</h3> All patients had active early RA and went on rapid escalation of treatment protocol [1]. Target of treatment was DAS28 &lt; 3.2. Treatment was started with methotrexate, escalating the dose from 15 to 25 mg over 8 weeks. Then hydroxycloroquine, leflunomide and biologic agents were successively added if the target of treatment was not achieved. Patients were reviewed every 4-6 weeks. Radiographs of hands and feet, HAQ score, patient-reported impact of the disease on everyday activities and employment status were taken at the first visit and after 1 year of treatment <h3>Results</h3> 79 patients have completed 1 year of treatment in the EAC. The female to male ratio was 1.7:1, and 78% of patients were seropositive. Disease activity and progression are shown in Table 1. <h3>Conclusions</h3> After 1 year of targeted protocol-driven treatment of early RA with conventional DMARDs, the majority of patients reported only minimal impact of the disease on everyday activities, retained their jobs and had significant improvement of HAQ score. Only 18% of patients developed new erosions, and only 11% of them needed biologic drugs. <h3>References</h3> Semenova O et al., Annals Rheum. Dis. 2012: 71, S3, 205. <h3>Disclosure of Interest</h3> None Declared
Sensory Threshold Testing
Authors: J Nico D De Neeling, Lex M Bouter, Robert J Heine
Journal: Diabetes Care (1993)

We read with much interest the recent study by Sosenko et al. (1). Studies that screen for both NIDDM and polyneuropathy in subjects without a history of glucose intolerance are rare and therefore welcome. In general, their cross-sectional data agree very well with our findings in a general Caucasian population. We also found that vibration threshold is related to glycemic level, controlling for age, height, and sex. In our study, this relationship persisted when we excluded diabetic subjects from
THE 4-YEAR PERCUTANEOUS CORONARY INTERVENTION CALIFORNIA AUDIT MONITORED PILOT WITH OFFSITE SURGERY (PCI-CAMPOS) OUTCOMES IN 205,052 PATIENTS IN HOSPITALS WITH AND WITHOUT ONSITE CARDIAC SURGERY
Authors: William J. Bommer, Suresh Ram, Zhongmin Li, Tanuj Patel, Geeta Mahendra, Laurie Vazquez, Jeffrey Southard
Journal: Journal of the American College of Cardiology (2015)
Commentary: Relevance of Risk Assessment to Exposed Communities
Authors: Carolyn Brickey
Journal: Environmental Health Perspectives (1995)

Current environmental policy tends to evaluate potential, theoretical exposure to health risks by evaluating one chemical or hazard at a time. Risk assessment techniques used by the U. S. Environmental Protection Agency (EPA) and other government agencies do not evaluate the cumulative impact of exposure to environmental contaminants. This problem is of particular significance to low-income and minority populations who tend to live in neighborhoods and work in locations that involve exposure to pollutants in air, water, and workplace activity. Certain areas within the border typify this lifestyle. The problem is further complicated by the fact that EPA operates separate programs for different media. Exposure patterns in the border suggest the need for a cross-media pollution prevention approach. Minority recruitment into health research, a coordination of research approaches and dollars, and new resources for effective monitoring of minority communities could provide a basic assessment of the risks and their sources. Further research into the cumulative impacts of prevalent subsets of chemicals is also needed. Recent efforts in the Great Lakes may pro? vide a model for this type of regional, cross-border effort. ? Environ Health Perspect 103(Suppl 1):89?91 (1995)