tbuckley/cabot-search huggingface dataset:
Pathologic Angiogenesis of Malignant Vascular Sarcomas: Implications for Treatment
Authors: Jalal A. Khan, Robert G. Maki, Vinod Ravi
Journal: Journal of Clinical Oncology (2017)

Angiosarcoma, epithelioid hemangioendothelioma, and Kaposi sarcoma are classified according to the line of differentiation that these neoplastic cells most closely resemble: the endothelial cell. Although these malignant vascular sarcomas demonstrate immunohistochemical and ultrastructural features typical of this lineage, they vary dramatically in presentation and behavior, reflecting oncologic mechanisms unique to each. Antineoplastic therapies offer significant benefit, but because of the rarity of these cancers, novel therapies are slow to develop, and treatment options for these cancers remain limited. Antiangiogenic approaches that have shown benefit in other malignancies have not fully realized their promise in vascular tumors, suggesting that these tumors do not depend entirely on either angiogenic growth factors or on neighboring endothelia that are affected by these agents. Nonetheless, translational studies have begun to unravel these distinct pathologies, identifying novel translocation products, targets of oncogenic virulence factors, and genomic mutations that hijack angiogenic signaling and drive malignant growth. Concurrently, an elaborate and highly regulated model of angiogenesis and lymphangiogenesis involving vascular endothelial growth factor-receptor tyrosine kinase and TGF-β and Notch pathways has emerged that informs treatment of these tumors as well as cancer in general. This review summarizes the literature on malignant vascular sarcomas in the context of current models of angiogenesis and, in light of recent clinical trial data, could help clinician-scientists generate novel therapeutic approaches.
Correlation of lactate dehydrogenase (LDH) isoenzyme profile with outcome in advanced colorectal cancer (CRC) patients (pts) treated with chemotherapy and bevacizumab (BEV) or cediranib (CED).
Authors: Jair Bar, Stuart Spencer, Shethah Morgan, Laura Pike, David Cunningham, Jane D Robertson, Juliane M Jürgensmeier, Glenwood D. Goss
Journal: Journal of Clinical Oncology (2012)

e13541 Background: There is a clinical need for predictive biomarkers of efficacy of VEGF signaling inhibitors (VSIs). LDH is a tetramer that can include any combination of the M and H subunits. LDH4 and 5 isoenzymes are composed mostly of the M subunit and are more abundant in hypoxic conditions. We speculated that the levels of LDH isoenzymes in pts serum may correlate with outcome of pts treated with VSIs. HORIZON I trial enrolled pts that were randomized to mFOLFOX6 with BEV or CED. A retrospective exploratory analysis was performed on baseline serum samples of these pts. Methods: Total serum LDH was tested on fresh samples during the conduct of the trial. About 2 years after the trial, frozen samples stored at -70 degrees were tested for total serum LDH and LDH isoenzymes, measured by agarose electrophoresis and a colorimetric enzymatic assay. Relative levels of M and H subunits were derived based on the known structure of each isoenzyme. Progression free survival (PFS) and overall survival (OS) were compared by subgroups of total LDH and LDH isoenzyme levels. P values were not calculated for these exploratory analyses. Results: Baseline total LDH levels from fresh serum were available for 207 pts. Total and isoenzyme LDH levels were available for frozen serum samples of 189 pts. Total LDH in the frozen and fresh samples correlated (R=0.9). Distant isoenzymes (e.g. LDH1 and 5) were negatively correlated. High M/H subunits ratio correlated with poor OS (HR=1.804, 95%CI 1.24-2.620). A non-significant trend for better OS to CED-treated vs. BEV-treated pts was seen in pts with high M/H ratio (e.g., CED 30mg vs BEV HR=0.685, 95%CI 0.382-1.23). Conclusions: Evaluation of LDH isoenzymes is feasible using serum samples kept frozen for 2 years. A negative correlation is seen between hypoxic-related and oxic-related isoenzymes. In CRC pts treated with a VSI, LDH isoenzyme hypoxia-associated profile correlates with poorer outcome. LDH isoenzyme profile as a possible predictive biomarker for benefit from CED vs. BEV requires further investigation.
Engineering Hydrogel Microenvironments to Recapitulate the Stem Cell Niche
Authors: Christopher M. Madl, Sarah C. Heilshorn
Journal: Annual Review of Biomedical Engineering (2017)

Stem cells are a powerful resource for many applications including regenerative medicine, patient-specific disease modeling, and toxicology screening. However, eliciting the desired behavior from stem cells, such as expansion in a naïve state or differentiation into a particular mature lineage, remains challenging. Drawing inspiration from the native stem cell niche, hydrogel platforms have been developed to regulate stem cell fate by controlling microenvironmental parameters including matrix mechanics, degradability, cell-adhesive ligand presentation, local microstructure, and cell–cell interactions. We survey techniques for modulating hydrogel properties and review the effects of microenvironmental parameters on maintaining stemness and controlling differentiation for a variety of stem cell types. Looking forward, we envision future hydrogel designs spanning a spectrum of complexity, ranging from simple, fully defined materials for industrial expansion of stem cells to complex, biomimetic systems for organotypic cell culture models.
Understanding barriers to receiving genetic testing after referral.
Authors: Drew Murray, Mounika Mandadi
Journal: Journal of Clinical Oncology (2017)

e13108 Background: About 5-10% of breast cancers are hereditary. Identifying women with hereditary breast and ovarian cancer syndromes helps implement screening strategies, chemoprevention regimens, preventative surgeries and identify family members at risk. Little is known about reasons for non-compliance with genetic testing after referral by an oncologist. To gain insight we investigated these barriers in a population of patients in Louisville, Kentucky. Methods: The study design was a IRB approved single institution retrospective analysis of all newly diagnosed breast cancer patients in the year 2014. Data on age, gender, race, education, insurance status, family history, referral orders and genetic testing results were analyzed for 204 patients. Characteristics of patients who received genetic testing after referral was made were compared to patients who did not receive genetic testing, despite referral. The categorical variables were compared using the Pearson Chi-square test for contingency tables while the t-test was used for continuous variables. Significance level was set at p≤0.05. All calculations are performed with SAS statistical software (SAS Institute Inc., Cary, NC). Results: Of 204 newly diagnosed breast cancer patients seen in 2014, 109 met NCCN guidelines for genetic testing. 89 total patients were referred for genetic testing. 67 patients received genetic testing after referral, while 22 patients did not receive the testing despite being referred. 29 patients met criteria for testing but were never referred. Statistical significance existed (P = 0.019) for the insurance status variable, those with private insurance being more likely to receive testing after being referred, and those without insurance being less likely to show up for genetic testing after being referred. There was no statistical significance for age(P = 0.787), race(P = 0.555), or education (P = 0.322). Conclusions: Being covered by private insurance was associated with increased completion of genetic testing after being referred by an oncologist. Age, race, and education did not impact the likelihood of receiving testing if referred. Further investigations will be made into reasons for non-referral in patients who met NCCN guidelines for testing.
Plasma levels of interleukin-33 (IL-33) and soluble suppression of tumorigenicity 2 (sST2) as a potential predictive biomarker in patients (pts) with advanced pancreatic ductal adenocarcinoma (PDAC) undergoing systemic chemotherapy (sCTX)
Authors: M. Kieler, M. Unseld, S. Demyanets, D. Bianconi, G. Prager
Journal: Annals of Oncology (2017)
Scale-Up of Voluntary Medical Male Circumcision Services for HIV Prevention — 12 Countries in Southern and Eastern Africa, 2013–2016
Authors: Jonas Z. Hines, Onkemetse Conrad Ntsuape, Kananga Malaba, Tiruneh Zegeye, Kennedy Serrem, Elijah Odoyo-June, Rose Kolola Nyirenda, Wezi Msungama, Kondwani Nkanaunena, Jotamo Come, Marcos Canda, Herminio Nhaguiombe, Ella K. Shihepo, Brigitte L.T. Zemburuka, Gram Mutandi, Emmanuel Yoboka, André H. Mbayiha, Hilda Maringa, Alfred Bere, J. Joseph Lawrence, Gissenge J.I. Lija, Daimon Simbeye, Kokuhumbya Kazaura, Ramadhani S. Mwiru, Stella Alamo Talisuna, Joseph Lubwama, Geoffrey Kabuye, James Exnobert Zulu, Omega Chituwo, Maybin Mumba, Sinokuthemba Xaba, John Mandisarisa, Brittney N. Baack, Lawrence Hinkle, Jonathan M. Grund, Stephanie M. Davis,, Carlos Toledo
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Countries in Southern and Eastern Africa have the highest prevalence of human immunodeficiency virus (HIV) infection in the world; in 2015, 52% (approximately 19 million) of all persons living with HIV infection resided in these two regions.* Voluntary medical male circumcision (VMMC) reduces the risk for heterosexually acquired HIV infection among males by approximately 60% (1). As such, it is an essential component of the Joint United Nations Programme on HIV/AIDS (UNAIDS) strategy for ending acquired immunodeficiency syndrome (AIDS) by 2030 (2). Substantial progress toward achieving VMMC targets has been made in the 10 years since the World Health Organization (WHO) and UNAIDS recommended scale-up of VMMC for HIV prevention in 14 Southern and Eastern African countries with generalized HIV epidemics and low male circumcision prevalence (3).† This has been enabled in part by nearly $2 billion in cumulative funding through the President's Emergency Plan for AIDS Relief (PEPFAR), administered through multiple U.S. governmental agencies, including CDC, which has supported nearly half of all PEPFAR-supported VMMCs to date. Approximately 14.5 million VMMCs were performed globally during 2008-2016, which represented 70% of the original target of 20.8 million VMMCs in males aged 15-49 years through 2016 (4). Despite falling short of the target, these VMMCs are projected to avert 500,000 HIV infections by the end of 2030 (4). However, UNAIDS has estimated an additional 27 million VMMCs need to be performed by 2021 to meet the Fast Track targets (2). This report updates a previous report covering the period 2010-2012, when VMMC implementing partners supported by CDC performed approximately 1 million VMMCs in nine countries (5). During 2013-2016, these implementing partners performed nearly 5 million VMMCs in 12 countries. Meeting the global target will require redoubling current efforts and introducing novel strategies that increase demand among subgroups of males who have historically been reluctant to undergo VMMC.
Use of PRO Measures to Inform Tolerability in Oncology Trials: Implications for Clinical Review, IND Safety Reporting, and Clinical Site Inspections
Authors: Janice Kim, Harpreet Singh, Kassa Ayalew, Kristina Borror, Michelle Campbell, Laura Lee Johnson, Alyson Karesh, Ni A. Khin, Joanne R. Less, Jerry Menikoff, Lori Minasian, Sandra A. Mitchell, Elektra J. Papadopoulos, Richard L. Piekarz, Kevin A. Prohaska, Susan Thompson, Rajeshwari Sridhara, Richard Pazdur, Paul G. Kluetz
Journal: Clinical Cancer Research (2017)

Cancer therapeutics frequently lead to symptomatic adverse events (AE) that can affect treatment tolerability. The NCI has developed the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) to assess symptomatic AEs by direct patient self-report. Although longitudinal assessment of patient-reported symptomatic AEs holds promise to better inform treatment tolerability, using patient-reported outcome (PRO) measures to assess symptomatic AEs has raised several regulatory and good clinical practice issues among those who conduct cancer clinical trials. These include concerns regarding trial monitoring, clinical review of PRO results by investigators and delegated clinical staff, whether PRO data on symptomatic AEs require investigational new drug (IND) safety reporting, and how the trial conduct and resultant PRO data will be assessed during clinical investigator site inspections. This article addresses current thinking regarding these issues in cancer clinical trials from the FDA, the NCI, and the Office for Human Research Protections. PRO measures, such as PRO-CTCAE, that assess symptomatic AEs in cancer trials are considered similar to other PRO assessments of symptoms, function, and health-related quality of life and can generate complementary data that may inform tolerability. Clarity on operational concerns related to incorporating PRO measures to inform tolerability is critical to continue the advancement of rigorous PRO assessment in cancer clinical trials. Clin Cancer Res; 24(8); 1780-4. ©2017 AACRSee related commentary by Nipp and Temel, p. 1777.
Abstract 14829: Prognostic Impact of Thrombus Burden as Evaluated by OCT in Patients With non-ST Elevation Acute Coronary Syndromes Undergoing PCI
Authors: Nassim Braik, Marion Chatot, Benjamin Bonnet, Fiona Ecarnot, Romain Chopard, Marc Badoz, Marie-France Seronde, Francois Schiele, Nicolas F Meneveau
Journal: Circulation (2016)

Introduction: We aimed to evaluate the impact of thrombus burden quantified by optical coherence tomography (OCT) on the risk of peri-procedural myocardial infarction (MI) (type IVa) in patients un...
Abstract 12579: Sirt2 Contributes to the Development of Heart Failure Through a Nrf2 Dependent Pathway
Authors: Xiaoyan Yang, Meng Shang, Christine Elizabeth Kamide, Chunlei Chen, Seong-Hoon Park, Rongxue Wu, Ting Liu, Athanassios Vassilopoulos, Hossein Ardehali
Journal: Circulation (2016)

Introduction: Heart failure is associated with a change in cardiac energy metabolism and increased oxidative stress. Sirtuins (SIRTs) are NAD+-dependent deacetylases, and critical regulators of energy metabolism and oxidative stress response. However, the function of SIRT2, the only cytosolic sirtuin protein, in regulating the development of heart failure is largely unknown. Methods and results: To explore the role of SIRT2 in the development of heart failure, we examined the response of Sirt2 -/- mice and their littermate controls to pressure overload by transverse aortic constriction (TAC) and cardiac ischemia/reperfusion (I/R). Sirt2 -/- mice had normal appearance and cardiovascular parameters at baseline. However, in response to TAC, Sirt2 -/- mice displayed resistance to the pathological hypertrophic response. In the I/R injury model, Sirt2 -/- mice had better cardiac function and less cardiac fibrosis after 28 days of surgeries compared to WT mice. In vitro , Sirt2 knockdown reduced reactive oxygen species (ROS) production and cell death in neonatal rat cardiomyocytes (NRCM) after H 2 O 2 treatment. Since cellular oxidative stress is a key contributing factor to both I/R and cardiac hypertrophy, and nuclear factor (erythroid-derived 2)-like 2 (NRF2) plays a major role in antioxidant activity of the cell through regulation of several antioxidant proteins, we tested whether NRF2 is involved in SIRT2-mediated cardiac response to oxidative stress. We found that NRF2 expression is higher in NRCM with Sirt2 knockdown compared to WT cells after H 2 O 2 stimulation. And NRF2 is translocated into the nucleus and its anti-oxidant target proteins are upregulated in NRCM with Sirt2 knockdown. Further experiments demonstrated that SIRT2 directly interacts with and deacetylates NRF2, and reduces its nuclear translocation and transcriptional activity. In addition, Sirt2 -/- mice have higher levels of acetylated NRF2 in the heart. Finally, knockdown of both Sirt2 and Nrf2 abrogates the effects of Sirt2 knockdown on ROS production and cellular damage. Conclusion: Our results indicate that SIRT2 contributes to the development of heart failure in mice, and promotes oxidative stress injury in cardiomyocytes by deacetylating NRF2 and altering its activity.
Association of Immunotherapy With Overall Survival in Elderly Patients With Melanoma
Authors: Marie Perier-Muzet, Elodie Gatt, Julien Péron, Claire Falandry, Mona Amini-Adlé, Luc Thomas, Stephane Dalle, Amelie Boespflug
Journal: JAMA Dermatology (2017)

Melanoma treatment has been revolutionized with the development of immune-based therapies that offer durable clinical responses in a subset of patients. Clinical outcomes after treatment by immunotherapy can be influenced by the host's immune system. The immune system is modified with age by age-related immune dysfunction.To evaluate if age influences clinical outcome and immune adverse events in patients treated by immunotherapy for metastatic melanoma.This was a single-center cohort analysis in patients treated with immunotherapy for metastatic melanoma between January 2007 and February 2016, in the Lyon Sud Hospital, France. A total of 92 patients with metastatic melanoma treated with ipilimumab, nivolumab, or pembrolizumab were retrospectively analyzed.Overall survival, progression-free survival, and immune-related adverse events were evaluated for each treatment line according to the patients' age.A total of 92 patients were eligible and included in this study for a total of 120 lines of treatment. Fifty-four patients were included in the cohort that was 65 years or younger (24 [44%] were female; mean [SD] age, 48.1 [12.5] years), and 38 patients were included in the cohort that was older than 65 years (12 [34%] were female; mean [SD] age, 74.8 [6.9] years). Mean follow-up duration starting at treatment initiation was 12.5 months. Patients older than 65 years treated with immunotherapy had a better mean progression-free survival (4.8 vs 3.4 months; P = .04) and overall survival (not reached vs 10.1 months; P = .009) than younger patients in univariate analysis, and after adjusting on prognosis covariates. This was particularly true with patients treated with anti-programmed cell death protein 1. Common immune-related adverse effects were similar in both cohorts.Age might be associated with a better clinical outcome after treatment with immunotherapy in the real-life setting. In our cohort, older patients did not have more immune-related adverse events. Further studies are warranted to confirm our results and describe the underlying mechanisms involved.
Disparities in all-cause mortality among younger commercially insured women with metastatic breast cancer.
Authors: Christine Leopold, Fang Zhang, Anita K. Wagner, Christine Y. Lu, Craig Earle, Dennis Ross-Degnan, James Frank Wharam
Journal: Journal of Clinical Oncology (2016)

e18069 Background: Though extensively studied in the Medicare population, little is known about disparities in mortality in younger women with metastatic breast cancer. Our aim was to examine whether overall survival differed by patient characteristics, region of residence, and time period of diagnosis. Methods: We examined administrative data (Optum; Eden Prairie, MN) of members insured through a large national US health insurer. Women with metastatic breast cancer were drawn from an open cohort of members aged 25 to 64 years enrolled between November 1, 2000, and December 31, 2008. Our outcome was time from incident metastatic breast cancer diagnosis to all-cause death, with up to 3 years of follow-up. We stratified by race, age at diagnosis, US region of residence, urban/rural residence, socio-economic status, Adjusted Clinical Groups (ACG) morbidity score, and time period of diagnosis. We constructed Kaplan-Meier survival plots and analyzed overall survival using multivariate Cox proportional hazard models. Results: Among 6694 women with incident metastatic breast cancer (73% white, 3% black, 23% other), 1184 women (18%) died within 3 years. We detected accelerated time to death among women residing in predominantly black versus white neighborhoods (adjusted hazard ratio, HR: 1.96; 95% confidence interval, CI: 1.44-2.67), women with high morbidity versus lower morbidity (HR: 1.30; 95% CI: 1.12-1.50), and women whose cancer was diagnosed during 2000-2004 versus 2005-2008 (HR: 1.55; 95% CI: 1.35-1.77). Women living in the Northeast region had longer overall survival compared with women living in the South (HR: 0.71; 95% CI: 0.55-0.92). Conclusions: In a cohort of younger commercially insured women with incident metastatic breast cancer, we detected disparities in survival by race, morbidity, and US region of residence. Incident diagnosis between 2005-2008 was associated with improved survival compared with 2000-2004. Research should look for modifiable factors that may explain these differences in survival.
Inspectors voice concern over independent residential detox units
Authors: Anne Gulland
Journal: BMJ (2017)

Independent residential detoxification units are putting patients at risk, with three out of four failing in at least one fundamental standard of care, the Care Quality Commission (CQC) has said.

In a briefing paper based on inspections of 68 residential detoxification units in the residential sector over the past two years, the commission said that it had uncovered “multiple concerns.”1

Some 49 out of the 68 units (72%) were found to be failing in at least one fundamental standard of care, the CQC warned.

Failure to provide safe care and treatment was …
COOH-terminal SAA1 peptides fail to induce chemokines but synergize with CXCL8 and CCL3 to recruit leukocytes via FPR2
Authors: Mieke De Buck, Mieke Gouwy, Nele Berghmans, Ghislain Opdenakker, Paul Proost, Sofie Struyf, Jo Van Damme
Journal: Blood (2017)
VE-Cadherin regulates the self-renewal of mouse embryonic stem cells via LIF/Stat3 signaling pathway
Authors: Ningning He, Xiaoniao Chen, Dan Wang, Ke Xu, Lingling Wu, Yuanyuan Liu, Hongyan Tao, Qinjun Zhao, Xiaocang Cao, Yuhao Li, Na Liu, Xin Qi, Zhongchao Han, Deling Kong, Jun Yang, Zongjin Li
Journal: Biomaterials (2017)
The Future of Radiology
Authors: Robert M. Schick
Journal: JAMA (2017)

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<i>Notes from the Field</i>: Absence of Asymptomatic Mumps Virus Shedding Among Vaccinated College Students During a Mumps Outbreak — Washington, February–June 2017
Authors: Jesse Bonwitt, Vance Kawakami, Adam Wharton, Rachel M. Burke, Neil Murthy, Adria Lee, BreeAnna Dell, Meagan Kay, Jeff Duchin, Carole Hickman, Rebecca J. McNall, Paul A. Rota, Manisha Patel, Scott Lindquist, Chas DeBolt, Janell Routh
Journal: MMWR Morbidity and Mortality Weekly Report (2017)