tbuckley/cabot-search huggingface dataset:
Preventing treatment failures in coronary artery disease: what can we learn from the biology of in-stent restenosis, vein graft failure, and internal thoracic arteries?
Authors: Cristiano Spadaccio, Charalambos Antoniades, Antonio Nenna, Calvin Chung, Ricardo Will, Massimo Chello, Mario F L Gaudino
Journal: Cardiovascular Research (2019)

Coronary artery disease (CAD) remains one of the most important causes of morbidity and mortality worldwide, and the availability of percutaneous or surgical revascularization procedures significantly improves survival. However, both strategies are daunted by complications which limit long-term effectiveness. In-stent restenosis (ISR) is a major drawback for intracoronary stenting, while graft failure is the limiting factor for coronary artery bypass graft surgery (CABG), especially using veins. Conversely, internal thoracic artery (ITA) is known to maintain long-term patency in CABG. Understanding the biology and pathophysiology of ISR and vein graft failure (VGF) and mechanisms behind ITA resistance to failure is crucial to combat these complications in CAD treatment. This review intends to provide an overview of the biological mechanisms underlying stent and VGF and of the potential therapeutic strategy to prevent these complications. Interestingly, despite being different modalities of revascularization, mechanisms of failure of stent and saphenous vein grafts are very similar from the biological standpoint.
Impact of autologous stem cell transplant in myeloma patients on renal function and overall survival.
Authors: Ala Abudayyeh, Maen Abdelrahim, Heather Y. Lin, Rima Saliba, Charles Martinez, Ruby Delgado, Valda D Page, Paul W Sanders, Muzaffar H. Qazilbash
Journal: Journal of Clinical Oncology (2019)

e19535 Background: Renal impairment has been negatively associated with progression free survival and overall survival in patients diagnosed with multiple myeloma (MM). Autologous stem cell transplant (ASCT) has become a standard of care for treatment in MM. Most previous studies have assessed the safety of ASCT and the improvement in renal function in patients with MM. However, a critical question about renal function over time, and its impact on survival after ASCT has rarely been addressed. In our study we sought to understand how renal function was impacted over time, the predictors of renal function, and overall survival after ASCT. Methods: We performed a retrospective review of all MM patients who underwent ASCT at MDACC from January1, 2008 through December 31, 2013. A total of 885 none dialysis patients who received Melphalan alone as the conditioning regimen were identified. We collected demographic information, ISS stage, and disease status at time of transplant and at last follow up. Creatinine, GFR (calculated using CKD Epi equation), calcium, and LDH were also collected at day 0, 100, 180, &amp; 365. Given the longitudinal nature of the data, linear mixed effect models were used to study the change of GFR over time. A joint model approach for longitudinal and survival data was used to assess association between overall survival and GFR with patient’s age at transplant, ISS, disease status, disease risk category and response to treatment prior to transplant included in the linear mixed effect models and hazard models. As sensitivity analyses, landmark analyses were conducted with day 0, 100, 180, and 365 days post-transplant as landmark time points. Results: Patients’ GFR at post-transplant time points were significantly higher (p ≤ 0.025) compared to the day of ASCT. A higher ISS stage at diagnosis was significantly associated with a lower GFR (p &lt; .0001) at all stages of chronic kidney disease. Specifically, compared to the patients with ISS stage I, those with ISS stage II or higher had lower GFR across all time points (p ≤ .0003). GFR value was not significantly associated with OS in any of the analyses described above. In contrast, disease status, ISS stage, response to induction prior to SCT were all associated with shorter OS. Conclusions: The study demonstrates in a large cohort and in a longitudinal manner that MM patients who underwent ASCT did not have further decline in GFR over time. In addition, GFR was strongly associated with ISS stage. As far as OS, MM-related factors significantly impacted the survival while GFR did not.
Dietary berries and ellagic acid diminish polar DNA adducts in ACI rats treated with 17β-estradiol
Authors: Harini S. Aiyer, Ramesh C. Gupta
Journal: Cancer Research (2004)

5499  Female hormone, 17β-estradiol (E2) is a known risk factor in the development of breast cancer. We have previously shown that due to redox cycling, Cu2+-mediated activation of 4-E2 produces polar oxidative DNA adducts, and that the adduct formation can be inhibited by known or potential antioxidants, including ellagic acid. Dietary administration of ellagic acid and raspberries, a rich source of ellagic acid, also reduced the baseline polar oxidative DNA adducts in CDl mice. In this study, we have tested the efficacy of different berries and ellagic acid on the modulation of polar oxidative adducts in E2-induced rat mammary tumorigenesis model. Female ACI rats were implanted with E2-filled silastic tubes. Animals (n = 4) were provided either control diet or diet supplemented with 2.5% powdered mixed berries (1:1 mixture of strawberries, raspberries, blueberries, blackberries and black raspberries), 2.5% blueberries, 2.5% blueberries plus ellagic acid (400 ppm), or ellagic acid (400 ppm). Animals received experimental diets 2 weeks prior to the implants and until the termination of the study. The animals were euthanized 60 d after the implant and the liver DNA was analyzed for polar DNA adducts by 32P-postlabeling adducteomics technology. Adducts were resolved in order of decreasing polarities and were categorized as: P-1, P-2, PL-1, PL-2 and L-1. Compared to the control diet, the adduct levels were significantly decreased by the test diets: The P-1 adducts were reduced by >75% with blueberries and >50% each with blueberries plus ellagic acid, and ellagic acid alone. Ellagic acid was more effective (60%) in diminishing the P-2 adducts, followed by blueberries, or blueberries plus ellagic acid (30-40 %). The mixed berries, however showed no change in the adduct levels. The less polar subgroup, PL-1 was also diminished with the test diets and the decline, in general, paralleled the decline observed for the more polar adducts. These results, especially with respect to ellagic acid, corroborate our earlier findings with the mice. Taken together, our data suggest that the newly discovered polar DNA adducts may, in part, originate from oxidative mechanisms, and their accumulation can be significantly prevented by dietary intervention. These findings may have a direct impact in elucidating the mechanism by which certain dietary principles inhibit carcinogenesis. (Supported by USPHS grant CA-90892.)
Analysis of platinum-based drug resistance gene expression in bladder cancer
Authors: Mariano Alvarez, Mariano Salibe, Guillermo Vila Ortiz, Martín Bercetche, Marcelo Rubinstein, Fernando Pitossi, Osvaldo Podhajcer
Journal: Cancer Research (2005)

767  The search for novel diagnostic tools in cancer based on gene expression studies often involves the comparison of malignant tumors and adjacent normal areas. It is estimated that malignant tumors may contain up to 10,000 gene mutations. Some of these mutations could be sensed as alarm signals during the 10 to 15 years of tumor development before it is clinically detected. Since homeostatic processes are under strict control by the CNS, we hypothesized that the CNS might sense tumor-triggered alarm signals during its initial development, before multiple mutations occur. We report here a microarray analysis of gene expression in different brain regions of syngeneic mice injected s.c. with either 4T1-mammary, LLC-6-lung or CT26-colon cancer cells. Mice were sacrificed 18 h, 72 h or 8 days after the initiation of the experiment. The transcriptional profile of the brain response to the presence of a peripheral tumor was analyzed using in house-printed 10 K oligonucleotide-based arrays. Since the magnitude of brain transcript changes using microarrays is generally modest, we performed a 4 - 5 replicates dye-swap design. Of the 10 K spots surveyed, we observed that 4.8% of genes were up-regulated and 6.6 % were down-regulated in mice bearing tumors (at least 1.15 fold difference and a p-value of less than 0.05). Analysis of 185 differentially expressed genes whose functional categories are known indicates a significant enrichment in genes related to synaptic activity and sickness behaviour. A subset of these genes was validated by Real Time PCR. By using a supervised pattern discovery algorithm (Genes@Work from IBM) and a cross-validation scheme we discriminated tumor-bearing mice from controls with 100% sensitivity and specificity. Moreover, we have also identified sets of brain-expressed genes suitable to discriminate between the three different cancer models. These findings indicate that neoplasia is early sensed by the CNS and suggest that the analysis of differentially expressed brain genes might aid to identify diagnostic molecules in peripheral blood.
Minimizing risk of bias in clinical implant research study design
Authors: Georgios A. Kotsakis
Journal: Periodontology 2000 (2019)

Abstract The field of clinical implant research has been flourishing in recent years. The number of related publications has been on the rise, as has the number of dental journals. However, the information gathered from surveillance studies on the quality of reporting and methodologic quality of published studies is unsettling. An important challenge faced by researchers endeavoring to conduct implant studies is how to factor the differences between implant surfaces and dental surfaces in the study design. Given the considerable experience that has been gained in the research methodology of the study of teeth and periodontal tissues, clinical implant research studies have often been conducted without giving much consideration to the fundamental differences between implants and teeth. This article discusses study design related to implant research in view of these differences. Observational and interventional study design methodology is discussed, and guidelines are provided to inform researchers on how to minimize bias in the design and implementation of these clinical studies when implant‐related outcomes are studied.
Evaluation of efficacy of serum and broncho-alveolar lavage Galactomannan estimation by ELISA in high-risk persistent febrile neutropenic patients
Authors: M. Sengar, L. Kumar, S. Thulkar, V. Kochupillai
Journal: Journal of Clinical Oncology (2006)

16505 Background: Chest infections constitute 36% of all infections in our acute leukemia patients. Conclusively establishing the diagnosis of invasive fungal aspergillosis (IPA), an important cause pulmonary infiltrates and mortality in high-risk febrile neutropenic patients, however, is difficult. We therefore evaluated the value of ELISA for Galactomannan (Gm) antigen and correlated the results with radiological findings. Methods: Twenty patients with persistent high-risk febrile neutropenia were assessed with chest X-ray, high resolution computed tomography (HRCT) chest and bronchoalveolar lavage (BAL) from the affected segment on day 5 of fever. Microbial cultures of blood, sputum and BAL and Galactomannan estimation in serum and BAL were done. IPA was defined as per the Mycoses Study Group criteria. Sensitivity, specificity and negative and positive predictive value of Galactomannan assay and diagnostic yield of each investigation was determined. Results: Diagnostic yield of CXR was 10%, blood culture, mainly gram negative bacilli, 15%, and BAL 20% (Aspergillus - 10%). Based on microbiology, radiology and cytopathology IPA was diagnosed in 16 cases (proven -1, probable -2, possible -13) and miliary tuberculosis, bacterial pneumonia and nocardiosis constituted the remaining. Nodules and halo sign were the most frequent (60%) CT findings in IPA. Sensitivity, specificity and positive and negative predictive value for serum were 78%, 100%, 100% and 64%, respectively, and for BAL, were 87.5%, 100%, 100% and 75%, respectively. Conclusions: CT-guided BAL and serial serum GM estimations are valuable non-invasive screening tools for IPA in high-risk persistent febrile neutropenic patients. No significant financial relationships to disclose.
Practical limitations of monocyte subset repartitioning by multiparametric flow cytometry in chronic myelomonocytic leukemia
Authors: Prateek A. Pophali, Michael M. Timm, Abhishek A. Mangaonkar, Min Shi, Kaaren Reichard, Ayalew Tefferi, Kevin Pavelko, Jose C. Villasboas, Dragan Jevremovic, Mrinal M. Patnaik
Journal: Blood Cancer Journal (2019)
PTEN loss as a context-dependent determinant of patient outcomes in obese and non-obese endometrioid endometrial cancer patients.
Authors: Zhenlin Ju, Shannon Neville Westin, Russell Broaddus, Jie Li, Navdeep Pal, Karen H. Lu, Robert L. Coleman, Samuel Klempner, Lewis Cantley, Gordon B. Mills, Andrea P. Myers
Journal: Journal of Clinical Oncology (2013)

5521 Background: Aberrations in the PI3K pathway, the central relay pathway of insulin signals, occur in the majority of endometrioid endometrial cancers. We explored the prognostic utility of PIK3CA, PIK3R1, and PTEN mutations, as well as PTEN protein loss, in the context of patient weight. Methods: Patients (pts) treated for endometrial cancer at a single institution between 2000 and 2009 were identified. Tumor DNA was extracted and exome sequencing performed using a 454 platform with confirmation of hot spot mutations by Sequenom. PTEN protein expression was determined by immunohistochemistry and reverse phase protein array (RPPA). RPPA for 135 relevant proteins was performed using a GeneTAC arrayer to create spot arrays. Slides were scanned, analyzed, and quantitated using Microvigene software. Results: One hundred eighty seven endometrioid endometrial cancer specimens were included. Median age was 61 yrs and median body mass index (BMI) was 33.5 kg/m 2 . The majority of pts had early stage (I/II) disease (74%) and grade 2 tumors (66%). There were no statistically significant associations between progression free survival (PFS) and PIK3CA, PIK3R1, PTEN mutation or loss. However, when stratified by BMI, PTEN loss was associated with a significantly improved PFS (p&lt; 0.006) in obese (BMI &gt; 30 kg/m 2 ) pts. In contrast, PTEN loss was associated with a worse PFS (p&lt;0.06) in non-obese (BMI &lt; 30 kg/m 2 ) pts. Further, PTEN loss in obese and non-obese pts resulted in distinct protein changes by RPPA, with canonical PI3K pathway activation observed only in the non-obese PTEN loss cohort. PTEN loss in obese pts was associated with decreased expression of CATENIN and phosphorylated FOXO3A. Conclusions: These data suggest the impact of PTEN loss on tumor biology and clinical outcomes must be interpreted in the context of BMI and provide potential explanation for prior discrepant findings on effect of PTEN status on prognosis in endometrial cancer. These data describe a clinically important interaction between metabolic state and tumor genetics that could potentially unveil the biologic underpinning of obesity-related cancers and may be relevant to ongoing clinical trials with PI3K pathway inhibitors.
Antiobesogenic effects of central GIPR antagonism
Authors: Jessica T.Y. Yue, Tony K.T. Lam
Journal: Journal of Clinical Investigation (2019)

Developing effective treatments for obesity and related metabolic disease remains a challenge. One logical strategy targets the appetite-regulating actions of gut hormones such as incretins. One of these incretins, glucose-dependent insulinotropic polypeptide (GIP), has garnered much attention as a potential target: however, whether it is beneficial to boost or block the action of GIP to promote weight loss remains an unresolved question. In this issue of the JCI, Kaneko and colleagues show that antagonizing GIP signaling in the CNS enhances the weight-reducing effects of leptin in rodents with diet-induced obesity. The authors posit that an increase in circulating intestinally derived GIP, as a consequence of overnutrition, acts in the brain to impair hypothalamic leptin action, resulting in increased food intake and body weight gain. This research advances the idea that multiple GIP signaling pathways and mechanisms exist in the obese state and offers intriguing insights into the antiobesogenic consequences of antagonizing brain GIP action.
The α-emitter astatine-211 targeted to CD38 can eradicate multiple myeloma in a disseminated disease model
Authors: Shyril O’Steen, Melissa L. Comstock, Johnnie J. Orozco, Donald K. Hamlin, D. Scott Wilbur, Jon C. Jones, Aimee Kenoyer, Margaret E. Nartea, Yukang Lin, Brian W. Miller, Theodore A. Gooley, Sherilyn A. Tuazon, Brian G. Till, Ajay K. Gopal, Brenda M. Sandmaier, Oliver W. Press, Damian J. Green
Journal: Blood (2019)
Perioperative covert stroke in patients undergoing non-cardiac surgery (NeuroVISION): a prospective cohort study
Authors: Marko Mrkobrada, Matthew T.V. Chan, David Cowan, Douglas Campbell, Chew Yin Wang, David Torres, German Malaga, Robert D. Sanders, Manas Sharma, Carl Brown, Alben Sigamani, Wojciech Szczeklik, Mukul Sharma, Gordon Guyatt, Eric E. Smith, Ronit Agid, Adam A. Dmytriw, Jessica Spence, Nikesh R. Adunuri, Flavia K. Borges, Timothy G. Short, Michael D. Hill, Feryal Saad, Ingrid Copland, Shirley Pettit, Quazi Ibrahim, Shrikant I. Bangdiwala, Salim Yusuf, Scott Tsai, Demetrios J Sahlas, Arun Mensinkai, Luciano A Sposato, Sara Hussain, Steven Yang, Deborah Siegal, Alexander Khaw, Jennifer Mandzia, Sara Simpson, Manoj Raval, Ahmer Karimuddin, PT Phang, Vincent CT Mok, William KK Wu, Simon CH Yu, Tony Gin, Pui San Loh, Mun Thing Liew, Norlisah Ramli, Yee Lein Siow, Maite Fuentes, Victor Ortiz-Soriano, Ellen Waymouth, Jonathan Kumar, Divya Sadana, Lenimol Thomas, Bogusz Kaczmarek, Heidi Lindroth, Daniel Sessler, Sarah Apolcer, Amelia Trombetta, Stephanie Handsor, Monidipa Dasgupta, John M Murkin, Shun Fu Lee, P.J. Devereaux
Journal: The Lancet (2019)
Incidence of Pediatric Cannabis Exposure Among Children and Teenagers Aged 0 to 19 Years Before and After Medical Marijuana Legalization in Massachusetts
Authors: Jennifer M. Whitehill, Calla Harrington, Cheryl J. Lang, Michael Chary, Waqaas A. Bhutta, Michele M. Burns
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Pediatric health care contacts due to cannabis exposure increased in Colorado and Washington State after cannabis (marijuana) policies became more liberal, but evidence from other US states is limited. <h3>Objective</h3> To document the incidence of pediatric cannabis exposure cases reported to the Regional Center for Poison Control and Prevention (RPC) before and after medical marijuana legalization (MML) in Massachusetts. <h3>Design, Setting, and Participants</h3> Cross-sectional comparison of pediatric cannabis exposure cases 4 years before and after MML in Massachusetts. The exposure cases included those of 218 children and teenagers aged between 0 and 19 years, as reported to the RPC from 2009 to 2016. Census data were used to determine the incidence. Data analysis was performed from November 12, 2018, to July 20, 2019. <h3>Exposure</h3> Cannabis products. <h3>Main Outcomes and Measures</h3> Incidence of RPC-reported cannabis exposure cases, both single substance and polysubstance, for the age group of 0 to 19 years, and cannabis product type, coingestants, and clinical effects. <h3>Results</h3> During the 8-year study period (2009-2016), the RPC received 218 calls involving cannabis exposure (98 single substance, 120 polysubstance) in children and teenagers aged 0 to 19 years, representing 0.15% of all RPC calls in that age group for that period. Of the total exposure cases, males accounted for 132 (60.6%) and females 86 (39.4%). The incidence of single-substance cannabis calls increased from 0.4 per 100 000 population before MML to 1.1 per 100 000 population after (incidence rate ratio, 2.4; 95% CI, 1.5-3.9), a 140% increase. The age group of 15 to 19 years had the highest frequency of RPC-reported cannabis exposures (178 calls [81.7%]). The proportion of all RPC calls due to single-substance cannabis exposure increased overall for all age groups from 29 before MML to 69 afterward. Exposure to edible products increased after MML for most age groups. <h3>Conclusions and Relevance</h3> Pediatric cannabis exposure cases increased in Massachusetts after medical marijuana was legalized in 2012, despite using childproof packaging and warning labels. This study provides additional evidence suggesting that MML may be associated with an increase in cannabis exposure cases among very young children, and extends prior work showing that teenagers are also experiencing increased cannabis-related health system contacts via the RPC. Additional efforts are needed to keep higher-potency edible products and concentrated extracts from children and teenagers, especially considering the MML and retail cannabis sales in an increasing number of US states.
Activation of eIF4E is increased dramatically in advanced prostate cancer and is inversely related to patient survival.
Authors: Jeremy Graff, Bruce Konicek, Rebecca Lynch, Ann McNulty, Stephen Parsons, Bruce Colligan, Larry Douglass, Julia Carter
Journal: Cancer Research (2007)

4063  eIF4E is the rate-limiting translation initiation factor governing the delivery of mRNA to ribosomes. eIF4E function is commonly enhanced in human and experimental cancers as a consequence of increased eIF4E expression or enhanced phosphorylation of the inhibitory eIF4E binding protein, 4EBP. Elevated eIF4E function preferentially enhances the translation of numerous potent growth and survival factors (e.g. c-myc, ODC, Cyclin D1). Accordingly, in experimental cancer models, eIF4E overexpression induces cellular transformation, tumorigenicity, invasion, metastasis and chemoresistance whereas eIF4E reduction can suppress malignancy. Increased eIF4E function has been demonstrated in human lymphomas and breast, head and neck, colon and bladder cancers. Moreover, eIF4E expression is consistently upregulated in metastases from numerous solid tumor types. Herein, we show for the first time that eIF4E function is elevated in human and experimental prostate cancers. In experimental prostate cancer models, eIF4E expression is increased specifically in hormone-refractory prostate cancer cells. In LNAI derivatives of LNCaP, 4EBP1 expression is reduced and the protein is hyperphosphorylated- a consequence of enhanced AKT signaling in LNAI cells. In hormone-refractory CWR22R xenograft tumors, the expression of eIF4E is increased relative to that in hormone- sensitive CWR22 tumors. In TRAMP transgenic tumors, eIF4E expression is also dramatically upregulated. Importantly, we also show that eIF4E function is elevated in human prostate cancer tissues. In a series of 140 prostate tissues, we show by immunohistochemistry that the levels of eIF4E and p4EBP1ser65 are substantially elevated in patients with advanced disease (≥ Gleason 7) (p
Abstract 18654: Metabolic Biomarkers Discriminate South Asian Patients With Coronary Artery Disease
Authors: Kristian C Becker, Damian Craig, Krishna Udayakumar, Rukmini Balu, Kuldeep Chahuan, Sanjay Mittal, Svati H Shah
Journal: Circulation (2017)

Introduction: Metabolic instability is a noted contributor to coronary artery disease (CAD). Prior metabolomic profiling studies in the mostly Caucasian CAD cohort, CATHGEN (Durham, NC) have offere...