tbuckley/cabot-search huggingface dataset:
The efficacy of preoperative metronomic therapy (MT) in luminal A locally advanced breast cancer.
Authors: Viacheslav Chubenko, Ludmila Zagorskaya, Anna Belyaeva, Robert Broyde, Iuliia Zaytseva, Elena Bit-sava, Vitaly Egorenkov, Ksenia Shelekhova, Vladimir Moiseyenko
Journal: Journal of Clinical Oncology (2018)

e12664 Background: The purpose of the breast cancer (BC) preoperative therapy (PT) is to achieve a complete pathological response (pCR) that correlates with overall survival or a decrease in its size for organ-preservation surgery. The hormonal therapy, dose-dense therapy or standard chemotherapy in patients (pts) with hormone-positive breast cancer (HR+ BC) allow to achieve the pCR only in 6% of cases. The biological features of luminal A tumor and the lack of an ideal predictive markers in terms of overall survival are the research basis for the additional treatment options. One of them is the use of MT, i.e. the chronic treatment of drugs low doses to affect either tumor cells or their microenvironment in order to change the natural history of breast cancer. Aim of this trial is to study the efficacy of MT in patients with luminal A locally advanced breast cancer in postmenopausal women. Methods: The study will enroll pts with locally advanced luminal A (ki67 less than 14%) breast cancer. The pts will receive 6 cycles of metronomic therapy preoperatively. Metronomic regimen includes fulvestrant 500 mg i.m. on days 1, 15, 29, and once monthly thereafter, capecitabine 500 mg x TID for 1 week q21 days p.o., bevacizumab 7.5 mg/kg Q3W i.v. The response evaluation will be assessed every 3 cycles of MT. All pts will undergo surgery after fully completed prescribed MT. Results: 15 postmenopausal pts were included in the study. The median age is 65 years. 14 patients are stage III, 1 – stage II. 60 % (9 out of 15) patients completed 6 cycles of treatment. In 53,3% (8 out of 15) pts mastectomy was performed. 9 pts were evaluable for response. Of these, 8 pts (88,8%) had partial response, 1 patient (11,2%) with stable disease. Another 6 pts are ongoing therapy and tumor efficacy results are not included in the efficacy evaluation. The treatment-related AEs are nausea gr 1 in 33% of pts and high blood pressure gr 2 in 22% pts. That resulted in discontinuation of bevacizumab (1 pts). The pts haven’t experienced hematological toxicity. Conclusions: The potential therapeutic efficacy of preoperative MT in pts with locally advanced luminal A is acceptable, and the overall benefit/risk assessment supports the proposed study design.
Concurrent intrathecal methotrexate and liposomal cytarabine for the treatment of leptomeningeal metastasis from solid tumors.
Authors: Brian J. Scott, Homira Feely, Tiffany Brown, Vincent Van Vugt, Ryan Kim, Paul Timothy Fanta, Lyudmila Bazhenova, Santosh Kesari
Journal: Journal of Clinical Oncology (2012)

2052 Background: Leptomeningeal metastasis (LM) from solid tumors is typically a late manifestation of disease with a median survival of weeks to a few months. Treatment is palliative, with no widely accepted standard of care. Options include intrathecal (IT) or systemic chemotherapy, radiation therapy or ventriculoperitoneal shunting. Randomized trials comparing single agent IT methotrexate to liposomal cytarabine have shown similar efficacy and tolerability. There is limited data, however, on the use of combination IT chemotherapy in solid tumor LM. Methods: We conducted a retrospective cohort study of 19 subjects treated for LM from solid tumors at a single institution. In addition to therapies directed at active solid tumor sites, each subject received IT liposomal cytarabine plus IT methotrexate injections every two weeks. Survival data and treatment-related toxicities were determined by systematic chart review. Results: LM was diagnosed by CSF cytology in 12/19 (63%), while the remainder were diagnosed by clinical and MRI findings. The most common cancer types were breast 7(37%), glioblastoma 6(32%) and lung 3(16%). The majority 18(95%) had active systemic or parenchymal brain disease at the time of treatment, requiring systemic chemotherapy 18(95%) or radiation therapy 13(68%). The median number of IT treatments was 4(range 1-9). Treatment was interrupted due to toxicity in 3(17%), while 7(37%) experienced ≥ CTCAE grade III toxicities, most commonly meningitis 3(16%). Treatment was stopped in 7/19(37%) following complete cytologic response 6/11(55%) or radiographic clearance 1/7(14%). The median overall survival was 96 days(n=6; range 29-158), median time to neurologic progression was 46 days (n=9; range 6-101) and the most common cause of death was progression of systemic disease 4(67%). Conclusions: Combination IT chemotherapy was reasonably well-tolerated, even in a population also receiving chemotherapy for progressive systemic disease. IT-related adverse events occurred at rates similar to previously reported single agent trials. Prospective evaluation is necessary to determine whether there is a survival benefit compared to single agent IT chemotherapy.
Functional role of BTB and CNC Homology 1 gene in pancreatic cancer and its association with survival in patients treated with gemcitabine
Authors: Xudong Huang, Jian Zheng, Jun Li, Xu Che, Wenle Tan, Wen Tan, Mingming Shao, Xinxin Cheng, Zhongli Du, Yanjie Zhao, Chengfeng Wang, Chen Wu, Dongxin Lin
Journal: Theranostics (2018)

Genetic variation (rs372883C/T) in the 3'-untranslated region of BTB and CNC homology 1 (BACH1) has been associated with pancreatic ductal adenocarcinoma (PDAC) risk in our previous genome-wide association study; however, the action roles of this genetic variation in PDAC remains unknown.Methods: BACH1 expression was measured by quantitative real-time PCR, Western blot and immunohistochemistry.The effects of BACH1 on cell proliferation and sensitivity to gemcitabine were examined by alteration of BACH1 expression in PDAC cells.Angiogenesis was determined in vitro using a human umbilical vein endothelial cell model.Reporter gene assays were conducted to compare the effects of microRNA-1257 on rs372883 variation.The associations between rs372883 variants and survival time in patients treated with gemcitabine were estimated by logistic regression.Results: We found substantially lower BACH1 expression in PDAC compared with normal pancreatic tissues and the rs372883T allele had significantly lower BACH1 levels than the rs372883C allele in both tumor and normal tissues.Knockdown of BACH1 expression provoked proliferation of PDAC cells and angiogenesis, which might result from upregulation of hemeoxygenase-1 that evokes oncogenic AKT and ERK signaling.The rs372883T>C change inhibits interaction of BACH1 with microRNA-1257, resulting in increased BACH1 expression.PDAC patients with the rs372883T allele were more resistant to gemcitabine and had shorter survival time compared with those with the rs372883C allele.Conclusion: These results shed light on the mechanism underlying the associations of BACH1 rs372883 variation with risk of developing PDAC and differential gemcitabine sensitivity in patients.
Lung screening in head and neck cancer survivors.
Authors: Avigayil East, Susan Swider
Journal: Journal of Clinical Oncology (2018)

179 Background: Lung screening is a relatively new screening method to detect early lung cancers among current or former smokers (American Cancer Society, 2016). One quarter of head and neck cancer survivors succumb to second malignancies with lung cancer representing 53% of second cancers (Baxi et al, 2014). At one ambulatory cancer center rates of screening within the head and neck cancer population were low at 15% (Local Tumor Registry, "Head and Neck Cases,” 2016). Furthermore, smoking documentation, which is required for determining appropriateness of lung screening, was incomplete within 39% of audited head and neck cancer patient charts (Local Tumor Registry, "Head and Neck Cases,” 2016). The objective of this project was to identify the effect of education on prescribers’ intention to screen and on smoking documentation within the electronic medical record. Methods: An educational session addressing barriers to screening prescription was presented to prescribers (N = 12) and clinical staff nurses (N = 18). Using an evidence-based approach, a question/answer period plus an electronic health record demonstration were included within the session (The Community Guide, 2017). The study design used pre- and posttest methodology to evaluate the session’s impact on screening rates, with pretest represented by extant data. Posttest survey and chart audits were used to measure outcomes of education including intention to screen and rates of completed smoking documentation. Results: Rates of completed smoking documentation increased from 61% to 78% after the educational intervention. On prescriber surveys 88% of respondents (N = 8) indicated that as a result of the educational session they were more likely to order lung screening. Other findings from survey showed there might have been a high level of knowledge about lung screening prior to the session. Conclusions: Multicomponent educational sessions served as a useful reminder resulting in high rates of intention to screen. Providing background information about lung screening may be useful for clinical nursing staff in improving smoking documentation. Next steps include a 6-month post hoc analysis of lung screening rates as well as nursing remediation to further increase smoking documentation.
Abstract 14696: The Risk of Atrial Fibrillation in Young Patients With Congenital Heart Disease in Sweden
Authors: Zacharias Mandalenakis, Annika Rosengren, Georgios Lappas, Peter Eriksson, Thomas Gilljam, Kristofer Skoglund, Maria Fedchenko, Per-Olof Hansson, Mikael Dellborg
Journal: Circulation (2016)

Introduction:  Patients with congenital heart disease (CHD) are assumed to be a vulnerable group for atrial fibrillation (AF) due to residual shunts, different vessel anatomy, progressive valvulopathy, hypertension and atrial scars from previous heart operations. However, the risk of developing AF in children and young adults with CHD compared to controls has not been established.   Hypothesis:  The aim of the present study was to estimate the risk of developing AF in children and young adults with CHD compared to matched controls.   Methods:  Data from the Swedish Patient and Cause of Death Registers were used in order to identify all patients with a CHD diagnosis who were born between 1970 and 1993. Diagnoses were coded according to the International Statistical Classification of Diseases (ICD 8 th , 9 th , and 10 th  editions). Each patient with CHD was matched by age, sex, and county with 10 controls from the Total Population Register in Sweden who were without any diagnosis of CHD. Follow-up and comorbidity data were collected until 2011.   Results:  Among 26,906 patients (51.3 % men) with CHD and 269,053 matched controls, 675 respective 449 developed AF; mean follow-up was 18.5 years. The risk to develop AF was 5.2 times higher (95% [CI] 3.3-8.4, p   Conclusions:  the risk of AF in children and young adults with CHD was approximately 5 times higher compared to matched controls. The patient group with the most complex congenital defects carried most of the risk and had a significantly 35 times higher risk of AF and could be considered for targeted intervention.
Elevated levels of circulating neutrophil extracellular traps and prothrombotic state after one dose of chemotherapy to predict doxorubicin cardiotoxicity in breast cancer.
Authors: Valentina K Todorova, Angela Pennisi, Issam Makhoul
Journal: Journal of Clinical Oncology (2018)

e12579 Background: Cardiotoxicity of doxorubicin (DOX) is dose-dependent, beginning with the first dose with subclinical myocardial injury that can progress to symptomatic heart failure months or years after infusion. It is important to be able to identify patients at risk during the early doses of chemotherapy. Neutrophil extracellular traps (NETs) contribute to the prothrombotic phenotype in cancer, which is further increased by chemotherapy. Alternatively, elevated levels of circulating exosomes with procoagulant potential were reported in patients with coronary syndromes. This study aimed to determine whether the circulating levels of NETs, exosomes and prothrombotic state can serve as potential biomarkers for presymptomatic DOX-induced cardiotoxicity in breast cancer patients. Methods: Blood samples were collected from breast cancer patients prior to and after the first cycle of DOX-based chemotherapy. Plasma samples of 15 patients who developed an abnormal decline of left ventricle ejection fraction (LVEF) after completion of chemotherapy and 15 patients who maintained normal LVEF were assayed for NETs markers, including dsDNA, histones and myeloperoxidase, thrombin-antithrombin (TAT) complex and exosomes. Results: The comparison of the changes in the plasma levels after one dose of DOX-based chemotherapy between the two groups of patients showed significantly elevated plasma levels of the NETs markers, exosomes and TAT complex in the group of patients who developed an abnormal decline of LVEF after the end of chemotherapy in comparison with patients who maintained normal LVEF. Conclusions: Our report provides evidence that plasma levels of NETs, prothrombotic state and exosomes are associated with presymptomatic DOX-cardiotoxicity after one dose of chemotherapy in breast cancer, and can serve as biomarkers for DOX cardiotoxicity. Further studies with larger cohort of patients can confirm the potential of these biomarkers to predict late DOX-associated cardiotoxicity and therefore help design treatments to reduce the incidence of the cardiotoxicity-associated morbidity and mortality, and improve survivorship.
Ubiquitination of ABCE1 by NOT4 in Response to Mitochondrial Damage Links Co-translational Quality Control to PINK1-Directed Mitophagy
Authors: Zhihao Wu, Yan Wang, Junghyun Lim, Boxiang Liu, Yanping Li, Rasika Vartak, Trisha Stankiewicz, Stephen Montgomery, Bingwei Lu
Journal: Cell Metabolism (2018)
Four evolutionary trajectories underlie genetic intratumoral variation in childhood cancer
Authors: Jenny Karlsson, Anders Valind, Linda Holmquist Mengelbier, Sofia Bredin, Louise Cornmark, Caroline Jansson, Amina Wali, Johan Staaf, Björn Viklund, Ingrid Øra, Anna Börjesson, Torbjörn Backman, Noémie Braekeveldt, Bengt Sandstedt, Niklas Pal, Anders Isaksson, Barbara Gürtl Lackner, Tord Jonson, Daniel Bexell, David Gisselsson
Journal: Nature Genetics (2018)
Associations between urban road-traffic emissions, health risks, and socioeconomic status in Ho Chi Minh City, Vietnam: a cross-sectional study
Authors: Linh Thi Phuong Le, Abraham Leung
Journal: The Lancet Planetary Health (2018)

BackgroundTailpipe emissions from road vehicles are an important cause of mortality in low-income cities. PM2·5 concentrations in Ho Chi Minh City (HCMC), Vietnam, are dangerously high, with mean annual concentrations of 17 230–560·88 μg/m3 (acceptable concentrations are 300 μg/m3 for 1 h a day maximum). Many studies have considered the health effects of air pollution. However, few studies have assessed the socio-spatial equity and health burden of traffic air pollution. Proximity to traffic has been associated with greater mortality. However, populations with lower socioeconomic statuses are more likely to be exposed to high concentrations of air pollution than are populations with higher socioeconomic statuses. We aimed to investigate whether the public health burden is associated with urban road-traffic emission in HCMC, and whether reducing air pollution will decrease hospital admissions, premature deaths, and years of life lost. We also explored the association between air pollution and socioeconomic status in HCMC.MethodsIn this cross-sectional study, we used the damage function approach in the Benefits Mapping and Analysis Program (BenMAP-Community Edition version 1.3) to estimate mortality risk and economic health burden resulting from PM2·5 emissions in HCMC. 2010–14 data from General Statistics Reports and the Vietnam Household Living Standard Survey, covering 19 districts and five suburban districts in HCMC, were analysed and mapped. A sensitivity analysis was also done to estimate the effects of air pollution reduction under different scenarios.FindingsWe estimated that emission of PM2·5 from on-road vehicles contributes to 780 (95% CI 340–1180) hospital admissions, 320 (240–570) premature deaths, and 4600 (3600–7600) years of life lost in HCMC each year. Motorcycles, trucks, and buses are the main sources of PM2·5 emission, associated with 210 (160–320) deaths each year. Populations with lower socioeconomic statuses are at higher risk of adverse health outcomes than are populations with higher socioeconomic statuses. Sensitivity analysis showed that reducing PM2·5 exposure by 5%, 10%, or 15% would result in fewer premature deaths and hospital admissions and a gain in life-years.InterpretationWe have developed a rapid and efficient method for estimating traffic air pollution risk, which can be applied to cities with similar settings to HCMC. The findings suggest that reducing motor vehicle emissions, particularly from motorcycles, trucks, and buses, could produce substantial health benefits. These findings call for better land-use and transport planning. Shifts in mode of transport from motor vehicles to public or active transport are urgently needed for urban areas in low-income countries.FundingNone.
Exercise capacity and quality of life in cancer survivors after completion of a survivorship focused exercise program.
Authors: Rebecca Jones, Trish Harrison, Doug Mesara
Journal: Journal of Clinical Oncology (2018)

169 Background: Exercise is a key component in addressing the concerns of cancer survivors. Only a third of survivors meet physical activity recommendations, and 70% of survivors are overweight/obese. For survivors, inactivity and obesity increase risks of recurrence, development of a second primary cancer, and higher mortality overall. Benefits of exercise include weight loss and improved quality of life. Survivorcise, a 12 week exercise program for survivors, was developed with the goal of improving exercise capacity and quality of life. Methods: Survivorcise is a small group exercise program meeting for 60 minutes, twice a week, for 12 weeks. Pre and post testing of strength, balance, and aerobic capacity and pre and post quality of life surveys were completed. Results: Forty-four participants completed Survivorcise between 2015 and 2017. Paired t-test analysis of pre and post testing revealed significant improvements in upper body strength (p = 0.0001), lower body strength (p = 0.0001), and balance (p = 0.0071). Aerobic capacity (p = 0.1583) improved, but not significantly. Paired t-test analysis of pre and post quality of life surveys revealed significant improvements in patient perception of strength (p = 0.0001), stress (p = 0.0002), weight gain (p = 0.0002), adjusting to the new normal (p = 0.0031), depression (p = 0.0034), fatigue (p = 0.0089), change in mood/behavior (p = 0.0094), pain (p = 0.0118), and lymphedema (p = 0.0290). Patient perception of memory (p = 0.1002), balance, walking, and mobility (p = 0.1104), sleep disturbance (p = 0.1361), neuropathy (p = 0.1455), anxiety (p = 0.1537), nausea/vomiting (p = 0.1597), hot flashes (p = 0.2247), poor appetite (p = 0.4560), osteoporosis (p = 0.5748), falls, tripping, and stumbling (p = 0.6574), and weight loss (p = 0.7890) showed no significant change. Conclusions: Our data demonstrated that Survivorcise is an effective tool for cancer survivors. The program significantly improved upper and lower body strength and balance. Participants self-reported significant improvement in perceived strength, stress, weight gain, adjusting to new normal, depression, fatigue, change in mood and behavior, pain, and lymphedema.
Abstract 15606: Comprehensive Prediction of Cardiac Outcomes in Pregnant Women With Heart Disease
Authors: Samuel C Siu, Jasmine Grewal, Mathew Sermer, Jennifer Mason, Marla Kiess, Rachel Wald, Jack Colman, Candice Silversides
Journal: Circulation (2017)

Introduction: Pregnant women with heart disease (HD) are at risk for maternal cardiac (CV) complications. Current risk scores for predicting CV complications in pregnancy are often used but have li...
Bombesein Staining May Be A Useful Marker In Idiopathic Interstitial Pneumonias Other Than Nehi
Authors: N. Emiralioglu, D. Orhan, N. Kiper, G. Cinel, G. Tugcu, E. Yalcin, D. Dogru, U. Ozcelik, M. Griese
Journal: American Journal of Respiratory and Critical Care Medicine (2016)
Association of Hydrochlorothiazide Use and Risk of Malignant Melanoma
Authors: Anton Pottegård, Sidsel Arnspang Pedersen, Sigrun Alba Johannesdottir Schmidt, Lisbet Rosenkrantz Hölmich, Søren Friis, David Gaist
Journal: JAMA Internal Medicine (2018)

Association of Hydrochlorothiazide Use and Risk of Malignant MelanomaWe have recently shown that hydrochlorothiazide use increases the risk of lip and nonmelanoma skin cancer, notably squamous cell carcinoma. 1,2It would have substantial implications if the carcinogenic effect of hydrochlorothiazide also extended to malignant melanoma.Methods | Similarly to our recent studies of hydrochlorothiazide, 1,2 we identified histologically verified melanoma cases (January 2004 to December 2015), each matched 1:10 (risk-set sampling; age, sex, and date) to cancerfree population controls.We required cases and controls to be between ages 18 and 90 years, without previous history of cancer (except nonmelanoma skin cancer), organ transplantation, HIV infection, or azathioprine use, and to have resided continuously in Denmark for 10 years.Using conditional logistic regression, we calculated odds ratios (ORs), with 95% CIs, for melanoma associated with cumulative hydrochlorothiazide use compared with never-use, adjusting for potential confounders (Table 1 and2).We performed stratified analyses by localization, stage, histologic subtype, and subgroups of age, sex, and history of nonmelanoma skin cancer.To evaluate potential confounding by indication, we performed analyses for other antihypertensive drugs, including bendroflumethiazide, angiotensin-converting enzyme inhibitors, angiontensin-II receptor antagonists, and calcium-channel blockers.