tbuckley/cabot-search huggingface dataset:
Maternal exposure to indole-3-carbinol during pregnancy and biomarkers of breast cancer risk among female rat offspring
Authors: Bin Yu, Anand Pria, Galam Khan, Aaron Foxworth, Jennifer Webster, Bill Helferich, Elliot Rosen, Leena Hilakivi-Clarke
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

696 

Maternal diet during pregnancy can have a permanent impact on offspring's later susceptibility to various diseases, including breast cancer. We investigated here, by utilizing an animal model, whether a maternal dietary exposure during pregnancy to 2,000 ppm indole-3-carbinol (I3C), present in cruciferous vegetables, impacts biological end-points that are associated with altered breast cancer risk among offspring. The end-points were mammary gland morphology, cell proliferation, and expression of genes in the Wnt/beta-catenin pathway that regulate mammary stem cell self-renewal and differentiation, were assessed when the offspring were 3- and 9-weeks of age. The number of terminal end buds (TEBs); i.e., the mammary structures that give rise to malignant mammary tumors, was significantly reduced in the rats exposed to I3C in utero , when compared to controls (p = 0.003). Further, cell proliferation was reduced in the lobules (p = 0.011), ducts (p = 0.038) and TEBs (p = 0.043), and cyclin D1 mRNA was down-regulated (p<0.008) in these rats. No changes in the estrogen receptor α or BRCA1 were noted. However, tumor suppressor gene APC mRNA was significantly down-regulated (p = 0.026), and in agreement with this finding, nuclear localization of β-catenin was increased in lobules (p = 0.036) in the in utero I3C exposed rats. Together, these data suggest that in utero I3C exposure is protective against breast cancer, but further research, including studying changes in susceptibility to mammary tumorigenesis (a study currently in progress), is necessary to confirm or refute this conclusion.
A pilot phase II clinical trial of the 20S proteasome inhibitor bortezomib in patients with relapsed malignant pleural mesothelioma
Authors: DA Fennell, Jan Van Meerbeeck, KJ O'Byrne, P Donnellan, S O'Reilly, R McDermott, L Mutti, G Gaudino, G Webb, S Jackson, M Parker, P Baas
Journal: Journal of Thoracic Oncology (2009)
Heparanase 2 Attenuates Head and Neck Tumor Vascularity and Growth
Authors: Miriam Gross-Cohen, Sari Feld, Ilana Doweck, Gera Neufeld, Peleg Hasson, Gil Arvatz, Uri Barash, Inna Naroditsky, Neta Ilan, Israel Vlodavsky
Journal: Cancer Research (2016)

The endoglycosidase heparanase specifically cleaves the heparan sulfate (HS) side chains on proteoglycans, an activity that has been implicated strongly in tumor metastasis and angiogenesis. Heparanase-2 (Hpa2) is a close homolog of heparanase that lacks intrinsic HS-degrading activity but retains the capacity to bind HS with high affinity. In head and neck cancer patients, Hpa2 expression was markedly elevated, correlating with prolonged time to disease recurrence and inversely correlating with tumor cell dissemination to regional lymph nodes, suggesting that Hpa2 functions as a tumor suppressor. The molecular mechanism associated with favorable prognosis following Hpa2 induction is unclear. Here we provide evidence that Hpa2 overexpression in head and neck cancer cells markedly reduces tumor growth. Restrained tumor growth was associated with a prominent decrease in tumor vascularity (blood and lymph vessels), likely due to reduced Id1 expression, a transcription factor highly implicated in VEGF-A and VEGF-C gene regulation. We also noted that tumors produced by Hpa2-overexpressing cells are abundantly decorated with stromal cells and collagen deposition, correlating with a marked increase in lysyl oxidase expression. Notably, heparanase enzymatic activity was unimpaired in cells overexpressing Hpa2, suggesting that reduced tumor growth is not caused by heparanase regulation. Moreover, growth of tumor xenografts by Hpa2-overexpressing cells was unaffected by administration of a mAb that targets the heparin-binding domain of Hpa2, implying that Hpa2 function does not rely on heparanase or heparan sulfate. Cancer Res; 76(9); 2791-801. ©2016 AACR.
Characterization of cultured mast cells derived from Ws/Ws mast cell- deficient rats with a small deletion at tyrosine kinase domain of c-kit
Authors: H Tei, T Kasugai, T Tsujimura, S Adachi, T Furitsu, K Tohya, M Kimura, KM Zsebo, GF Newlands, HR Miller
Journal: Blood (1994)
<i>R2d2</i>Drives Selfish Sweeps in the House Mouse
Authors: John P. Didion, Andrew P. Morgan, Liran Yadgary, Timothy A. Bell, Rachel C. McMullan, Lydia Ortiz de Solorzano, Janice Britton-Davidian, Carol J. Bult, Karl J. Campbell, Riccardo Castiglia, Yung-Hao Ching, Amanda J. Chunco, James J. Crowley, Elissa J. Chesler, Daniel W. Förster, John E. French, Sofia I. Gabriel, Daniel M. Gatti, Theodore Garland, Eva B. Giagia-Athanasopoulou, Mabel D. Giménez, Sofia A. Grize, İslam Gündüz, Andrew Holmes, Heidi C. Hauffe, Jeremy S. Herman, James M. Holt, Kunjie Hua, Wesley J. Jolley, Anna K. Lindholm, María J. López-Fuster, George Mitsainas, Maria da Luz Mathias, Leonard McMillan, Maria da Graça Morgado Ramalhinho, Barbara Rehermann, Stephan P. Rosshart, Jeremy B. Searle, Meng-Shin Shiao, Emanuela Solano, Karen L. Svenson, Patricia Thomas-Laemont, David W. Threadgill, Jacint Ventura, George M. Weinstock, Daniel Pomp, Gary A. Churchill, Fernando Pardo-Manuel de Villena
Journal: Molecular Biology and Evolution (2016)

A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether “selfish” genes are capable of fixation—thereby leaving signatures identical to classical selective sweeps—despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2HC) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2HC rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2HC is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution.
Optimizing Treatment Risk and Benefit for Elderly Patients With Advanced Non–Small-Cell Lung Cancer: The Right Treatment for the Right Patient
Authors: Carolyn J. Presley, Cary P. Gross, Rogerio C. Lilenbaum
Journal: Journal of Clinical Oncology (2016)

The Oncology Grand Rounds series is designed to place original reports published in theJournal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published inJournal of Clinical Oncology, to patients seen in their own clinical practice.A 78-year-old woman with a 40-pack-year smoking history has been referred for treatment of advanced non-small-cell lung cancer. She presented with a persistent cough and worsening dyspnea on exertion. A chest x-ray followed by a chest computed tomography scan revealed a 3-cm right upper lobe mass along with a moderate-size pleural effusion. Pleural fluid cytology was positive for adenocarcinoma. A brain magnetic resonance imaging scan was negative. A reflex molecular profile, includingKRAS,EGFR,ALK,BRAF,HER2,RET,MET, andROS, did not reveal an actionable abnormality. Her past medical history includes diabetes, hypertension, and osteopenia. Her medications include a β-blocker, angiotensin-converting enzyme inhibitor, oral antidiabetic agent, calcium, and vitamin D. The laboratory evaluation is notable for a hemoglobin of 10.8 g/dL and a creatinine clearance of 36 mL/min. The other laboratories are within normal limits. She is somewhat limited by the shortness of breath but maintains an Eastern Cooperative Oncology Group performance status of 1. She is independent in all of her instrumental and basic activities of daily living and denies falls. She has been referred to discuss treatment options.
Some Electrical Properties of Chemically Induced Tumor Cells 2
Authors: Tushar K. Chowdhury, Alec C. Chou
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Some Electrical Properties of Chemically Induced Tumor Cells Get access Tushar K. Chowdhury, Tushar K. Chowdhury 3Department of Physiology and Biophysics, University of Oklahoma Health Sciences Center, Oklahoma City, Okla Search for other works by this author on: Oxford Academic PubMed Google Scholar Alec C. Chou Alec C. Chou Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 6, December 1973, Pages 1981–1982, https://doi.org/10.1093/jnci/51.6.1981 Published: 01 December 1973 Article history Received: 21 May 1973 Accepted: 17 September 1973 Published: 01 December 1973
Reduced Racial Disparity in Kidney Transplant Outcomes in the United States from 1990 to 2012
Authors: Tanjala S. Purnell, Xun Luo, Lauren M. Kucirka, Lisa A. Cooper, Deidra C. Crews, Allan B. Massie, L. Ebony Boulware, Dorry L. Segev
Journal: Journal of the American Society of Nephrology (2016)

Earlier studies reported inferior outcomes among black compared with white kidney transplant (KT) recipients. We examined whether this disparity improved in recent decades. Using the Scientific Registry of Transplant Recipients and Cox regression models, we compared all-cause graft loss among 63,910 black and 145,482 white adults who received a first-time live donor KT (LDKT) or deceased donor KT (DDKT) in 1990–2012. Over this period, 5-year graft loss after DDKT improved from 51.4% to 30.6% for blacks and from 37.3% to 25.0% for whites; 5-year graft loss after LDKT improved from 37.4% to 22.2% for blacks and from 20.8% to 13.9% for whites. Among DDKT recipients in the earliest cohort, blacks were 39% more likely than whites to experience 5-year graft loss (adjusted hazard ratio [aHR], 1.39; 95% confidence interval [95% CI], 1.32 to 1.47; P &lt;0.001), but this disparity narrowed in the most recent cohort (aHR, 1.10; 95% CI, 1.03 to 1.18; P =0.01). Among LDKT recipients in the earliest cohort, blacks were 53% more likely than whites to experience 5-year graft loss (aHR, 1.53; 95% CI, 1.27 to 1.83; P &lt;0.001), but this disparity also narrowed in the most recent cohort (aHR, 1.37; 95% CI, 1.17 to 1.61; P &lt;0.001). Analyses revealed no statistically significant differences in 1-year or 3-year graft loss after LDKT or DDKT in the most recent cohorts. Our findings of reduced disparities over the last 22 years driven by more markedly improved outcomes for blacks may encourage nephrologists and patients to aggressively promote access to transplantation in the black community.
Prophylactic efficacy of phenelzine and imipramine in chronic atypical depression: likelihood of recurrence on discontinuation after 6 months' remission
Authors: J W Stewart, E Tricamo, P J McGrath, F M Quitkin
Journal: American Journal of Psychiatry (1997)

Objective: Demonstration of antidepressant efficacy beyond 6 months has infrequently been addressed, and no long-term efficacy data exist for patients with chronic atypical depression.Method: Sixty patients with atypical depression (according to Columbia University criteria) of at least 2 years' duration and who had improved with imipramine or phenelzine were stabilized for 6 months and then randomly continued the same medication or placebo for 6 months.Results: Several baseline differences suggested that patients who entered the discontinuation trial on a regimen of phenelzine were more chronically depressed than the imipramine-treated patients.Survival analysis showed a marked advantage for phenelzine relative to placebo.In addition, patients switched to placebo from phenelzine experienced a recurrence of depressive symptoms significantly more often than patients switched to placebo from imipramine.Patients maintained with imipramine did not have lower relapse rates than those switched from imipramine to placebo.Recurrence rates were 23% for patients maintained on a regimen of phenelzine, 41% for those maintained on a regimen of imipramine, 47% for those switched from imipramine to placebo, and 87% for placebo-treated patients originally treated with phenelzine.Conclusions: Patients with chronic atypical depression are at high risk of recurrence if phenelzine is withdrawn 6 months after initial improvement.Similar findings were not demonstrated for imipramine; this replicates acute trials demonstrating imipramine's relative ineffectiveness in patients with atypical depression.Differences in recurrence rates after the switch to placebo from phenelzine and imipramine could be due to the two drugs' different mechanisms of action or to baseline differences in the two populations.
ATPS-04REPURPOSING PHENFORMIN FOR THE TREATMENT OF GLIOBLASTOMA: ROLE OF THE H19/LET-7/STAT3 AXIS
Authors: Wei Jiang, Simona Cazacu, Cunli Xiang, Ziv Brodie, David Shackelford, Chaya Brodie
Journal: Neuro-Oncology (2015)

Glioblastoma (GBM) are characterized by an infiltrative nature and high resistance to radio- and chemotherapy. Despite advances in novel therapeutic approaches, the median survival of 12-14 months has not changed significantly. Therefore, there is an imperative need for the identification of alternative therapeutic approaches. The anti-diabetic biguanide drug metformin has been reported to exert anti-tumor effects. Phenformin, a metformin analog, is a more potent inhibitor of tumor growth, especially for Liver Kinase B1-deficient tumors. Our study demonstrates, for the first time, the effect of phenformin on the stemness and apoptosis of glioma cells and glioma stem cells (GSCs). We found that phenformin inhibited the self-renewal of GSCs, decreased the expression of the stemness markers, CD44 and Sox2 and the mesenchymal transformation of these cells. Phenformin at higher concentrations also induced apoptosis in both GSCs and differentiated glioma cells. The expression of AMPK and the phosphorylation of this kinase in response to phenformin were relatively low in GSCS, suggesting that this drug impacted the self-renewal and apoptosis of these cells mostly in an AMPK-independent manner. Phenformin inhibited the STAT3 pathway and its effects on GSCs were further enhanced by STAT3 inhibitors. In addition, phenformin decreased the expression of the long non-coding RNA, H19 and increased the expression of miR-124 and Let-7 and silencing of these miRNAs abrogated phenformin effects. Combined treatment of phenformin with radiation and temozolomide exerted a synergistic anti-tumor effects on GSCs which were more significant than those exerted by combined treatments with metformin. Using GSC-derived xenografts we demonstrated that phenformin inhibited tumor growth and angiogenesis, increased cell apoptosis and prolonged the overall survival of mice bearing GSC-derived xenografts. Our results demonstrate that phenformin can target GSCs via the STAT3/H19/Let7 axis and can be efficiently combined with current therapies for the treatment of GBM and the eradication of GSCs.
Oral Buflomedil in the Prevention of Cardiovascular Events in Patients With Peripheral Arterial Obstructive Disease
Journal: Circulation (2008)

Cardiovascular-related morbidity and mortality in patients with peripheral arterial obstructive disease remain high. We performed an international, multicenter, randomized, double-blind, placebo-controlled trial to investigate whether long-term administration of oral buflomedil could reduce the rate of cardiovascular events in patients with intermittent claudication.Patients >40 years of age with documented peripheral arterial obstructive disease, intermittent claudication, and an ankle-brachial index between 0.30 and 0.80 were eligible for inclusion and were randomized to receive orally either buflomedil or placebo for 2 to 4 years. Aspirin was recommended for all patients (unless they were receiving other antithrombotic treatments at inclusion). The primary efficacy outcome was critical cardiovascular events, defined as the composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, symptomatic deterioration of peripheral arterial obstructive disease, or leg amputation. A total of 2078 patients were recruited. Mean treatment duration was 33 months. The rate of critical cardiovascular events was significantly lower in buflomedil-randomized patients than in placebo-randomized patients (9.1% versus 12.4%; hazard ratio, 0.742; 95% confidence interval, 0.603 to 0.915; P=0.0163). Ankle-brachial index increased by 9.2% in buflomedil-randomized patients and decreased by 3.6% in placebo-randomized patients (P<0.001). Tolerance of buflomedil and placebo was comparable.Compared with placebo, buflomedil administered for 3 years reduced the occurrence of symptomatic cardiovascular events by 26%. The main contributor to the difference in the composite outcome was the reduction in symptomatic deterioration of peripheral arterial disease. The use of buflomedil should be considered in addition to an antiplatelet agent in patients with peripheral arterial obstructive disease and intermittent claudication.
Abstract 250: Pericardial Grafting Of Cardiac Progenitor Cells In The Three-dimensional Thick Scaffold Improves Cardiac Function After Myocardial Infarction In Mice.
Authors: Naomichi Kondo, Toshio Nagai, Mei-Lan Liu, Toshinao Takahashi, Masato Kanda, Katsuhisa Matsuura, Issei Komuro, Yoshio Kobayashi
Journal: Circulation Research (2014)

Cardiac progenitor cell (CPC) therapy for heart disease has been examined enthusiastically. However, optimal scaffolds which maintain the transplanted cells are still elusive. We used clonally expanded stem cell antigen 1-positive CPCs from adult mice and produced a three-dimensional thick scaffold (CPC-scaffold), in which CPCs were cultivated up to 2 month with self-assembling peptide RADA16-I. Addition of designer self-assembling peptide containing the active motifs of 2-unit RGD binding sequence and IGF-1 promoted three-dimensional spreading and viability of CPCs. After making myocardial infarction (MI) with left coronary artery ligation in mice, we transplanted CPC-scaffold on the surface of infarction area and confined it inside of the pericardial space by closing parietal pericardium. Four weeks after transplantation, echocardiography showed that FS of treatment group (16±10%, n=17) was higher than that of control (MI only) group (10±6.8%, n=19) (P&lt;0.05) and that LVDd of treatment group (5.4±1.0mm, n=17) was smaller than that of control group (6.2±1.1mm, n=19) (P&lt;0.05). Infarction area was significantly decreased in treatment group (46±21%, n=17), compared to control group (59±19%, n=18) (P&lt;0.05). Immunohistochemical staining for von-Willebrand factor (vWF) showed that the number of vWF-positive capillaries per mm2 in treatment group (16.8±3.2, n=5) was higher than that of control group(8.9±3.4, n=5) (P&lt;0.05). There were many of CD31-positive capillaries with or without α-smooth muscle cell actin-expressing perivascular cells in the graft area. By using fluorescent-conjugated avidin, biotin-labeled scaffold was globally detected in the graft area 1 week after transplantation, but sparsely 4weeks after, suggesting that the transplanted scaffold was biodegradable. To examine whether transplanted CPCs remain in the scaffold, we labeled CPCs with red fluorescence protein (RFP). RFP+CPCs were observed in the graft area 4 weeks after transplantation of RFP+CPC-scaffold. FISH analysis showed that sex-mismatched CPCs were globally detected in the graft area on the surface of the heart. Therefore pericardial grafting of well-vascularized and cellularized CPC-scaffold was a useful method to improve cardiac function after MI.
Endotypes of pollen‐food syndrome in children with seasonal allergic rhinoconjunctivitis: a molecular classification
Authors: C. Mastrorilli, S. Tripodi, C. Caffarelli, S. Perna, A. Di Rienzo‐Businco, I. Sfika, R. Asero, A. Dondi, A. Bianchi, C. Povesi Dascola, G. Ricci, F. Cipriani, N. Maiello, M. Miraglia Del Giudice, T. Frediani, S. Frediani, F. Macrì, C. Pistoletti, I. Dello Iacono, M. F. Patria, E. Varin, D. Peroni, P. Comberiati, L. Chini, V. Moschese, S. Lucarelli, R. Bernardini, G. Pingitore, U. Pelosi, R. Olcese, M. Moretti, A. Cirisano, D. Faggian, A. Travaglini, M. Plebani, M. C. Verga, M. Calvani, P. Giordani, P. M. Matricardi
Journal: Allergy (2016)

Pollen-food syndrome (PFS) is heterogeneous with regard to triggers, severity, natural history, comorbidities, and response to treatment. Our study aimed to classify different endotypes of PFS based on IgE sensitization to panallergens.We examined 1271 Italian children (age 4-18 years) with seasonal allergic rhinoconjunctivitis (SAR). Foods triggering PFS were acquired by questionnaire. Skin prick tests were performed with commercial pollen extracts. IgE to panallergens Phl p 12 (profilin), Bet v 1 (PR-10), and Pru p 3 (nsLTP) were tested by ImmunoCAP FEIA. An unsupervised hierarchical agglomerative clustering method was applied within PFS population.PFS was observed in 300/1271 children (24%). Cluster analysis identified five PFS endotypes linked to panallergen IgE sensitization: (i) cosensitization to ≥2 panallergens ('multi-panallergen PFS'); (ii-iv) sensitization to either profilin, or nsLTP, or PR-10 ('mono-panallergen PFS'); (v) no sensitization to panallergens ('no-panallergen PFS'). These endotypes showed peculiar characteristics: (i) 'multi-panallergen PFS': severe disease with frequent allergic comorbidities and multiple offending foods; (ii) 'profilin PFS': oral allergy syndrome (OAS) triggered by Cucurbitaceae; (iii) 'LTP PFS': living in Southern Italy, OAS triggered by hazelnut and peanut; (iv) 'PR-10 PFS': OAS triggered by Rosaceae; and (v) 'no-panallergen PFS': mild disease and OAS triggered by kiwifruit.In a Mediterranean country characterized by multiple pollen exposures, PFS is a complex and frequent complication of childhood SAR, with five distinct endotypes marked by peculiar profiles of IgE sensitization to panallergens. Prospective studies in cohorts of patients with PFS are now required to test whether this novel classification may be useful for diagnostic and therapeutic purposes in the clinical practice.