tbuckley/cabot-search huggingface dataset:
Does the translocation of human ribosomal protein S3 (hS3) to the nucleus under conditions of oxidative stress pose a threat to the efficient repair of damaged DNA bases
Authors: Vijay Hegde, Sridevi Yadavilli, Walter Deutsch
Journal: Cancer Research (2008)

3140  The human ribosomal protein S3 (hS3) possesses roles in extra ribosomal activities that influence DNA repair, cancer metastasis and apoptosis beyond its participation in protein synthesis. One example of such activity is the processing of oxidative DNA damage. Several DNA modifications are formed under conditions of oxidative stress, most common being 7, 8-dihydro-8-oxoguanine (8-oxoG), which if not repaired, results in G:C to T:A transversion mutations. The removal of 8-oxoG in humans is not as robust as seen in other organisms as the specific 8-oxoG DNA glycosylase/AP lyase (hOGG1) that initiates the base excision repair (BER) of 8-oxoG is relatively inefficient because of high affinity for the product of the reaction it catalyses. Our in vitro studies using surface plasmon resonance (SPR) technology have shown that hS3 has an extraordinarily high binding affinity for 8-oxoG and abasic sites in DNA. Additionally, pre-incubation of hS3 with a 37mer oligonucleotide containing 8-oxoG inhibited the removal of this lesion by OGG1, thereby suggesting that hS3 is creating an obstacle to the efficient repair of 8-oxoG. In agreement with this hypothesis are studies that show that the knockdown of hS3 expression by RNA interference in HEK293 cells resulted in increased cell survival in the presence of DNA damaging agents. Recent data from our lab also demonstrated a significant portion of cytoplasmic hS3 is translocated to the nucleus in cells exposed to genotoxic agents, showing that in fact hS3 is poised to carry out a role involving BER.  The ability of hS3 to presumably block the liberation of 8-oxoG has led us to question what effect hS3 expression has in vivo on the whole animal. We have created mice that over express hS3 and are testing the hypothesis that, “Under conditions of oxidative stress cytoplasmic hS3 translocates to the nucleus and binds to 8-oxoG residues in DNA, blocks its repair and affects cell survival and/or tumorigenesis in vivo”. Observations made in these mice should be informative to understand the role of this protein in the oxidative stress induced DNA damage response pathway and its potential involvement in cancer etiology.
Disruption of protocadherin function as an indicator of cancer progression.
Authors: James Shima, Joseph Delaney, Anita Umesh, Jenny Park, Gregory Wall, Qiaojuan Su, Mamatha Shekar, Ilya Kupershmidt
Journal: Journal of Clinical Oncology (2012)

e21159 Background: Protocadherins (PCDH) are a large family of calcium-dependent cell–cell adhesion molecules that are involved in tissue morphogenesis, in particular the development of the central nervous system. Recently, alteration of PCDH alpha/beta/gamma locus genes have been implicated in a number of oncogenic processes: hypermethylation of the PCDH locus in Wilms’ tumor progression and metastasis, differential expression of some PCDH genes between bone and brain metastases in breast cancer patients, and epigenetic silencing of PCDH gamma A11 in astrocytoma invasion of the adjacent parenchyma. Assessment of PCDH function could help guide treatment decisions by aiding in the identification of cancer patients who are more likely to develop metastases. Methods: Identification of altered PCDH locus genes in cancer patient samples was performed using the NextBio platform which incorporates curated public genomic data from numerous sources, including TCGA, GEO, COSMIC, and others. Correlation of numerous data types was used to identify deleterious mutations, altered RNA expression, and copy number changes that were indicative of metastasis or a more advanced disease state. Results: A nearly 3-fold increase in the frequency of potentially detrimental somatic mutations in the PCDH gamma locus was observed in breast and ovarian cancer patients with extensive lymph node metastases (N3) compared to patients with a lower degree of lymph node metastasis (N0-N2). Similarly, expression of PCDH locus genes was down-regulated in cases of lymphoma, in metastatic samples across a number of diseases, and in diseases that commonly result in lymph node metastases including breast and lung cancer. Conclusions: Stratification of patient subgroups based on molecular signatures has become increasingly important for both assigning patients to appropriate clinical trials as well as providing insight into effective treatment options. Examination of PCDH perturbations may provide insight into a patient’s risk of developing a metastatic disease, in particular metastases to lymph nodes, and help identify patients who may benefit from a more aggressive treatment regimen.
Detection of glaucomatous optic neuropathy with spectral-domain optical coherence tomography: a retrospective training and validation deep-learning analysis
Authors: An Ran Ran, Carol Y Cheung, Xi Wang, Hao Chen, Lu-yang Luo, Poemen P Chan, Mandy O M Wong, Robert T Chang, Suria S Mannil, Alvin L Young, Hon-wah Yung, Chi Pui Pang, Pheng-Ann Heng, Clement C Tham
Journal: The Lancet Digital Health (2019)

BackgroundSpectral-domain optical coherence tomography (SDOCT) can be used to detect glaucomatous optic neuropathy, but human expertise in interpretation of SDOCT is limited. We aimed to develop and validate a three-dimensional (3D) deep-learning system using SDOCT volumes to detect glaucomatous optic neuropathy.MethodsWe retrospectively collected a dataset including 4877 SDOCT volumes of optic disc cube for training (60%), testing (20%), and primary validation (20%) from electronic medical and research records at the Chinese University of Hong Kong Eye Centre (Hong Kong, China) and the Hong Kong Eye Hospital (Hong Kong, China). Residual network was used to build the 3D deep-learning system. Three independent datasets (two from Hong Kong and one from Stanford, CA, USA), including 546, 267, and 1231 SDOCT volumes, respectively, were used for external validation of the deep-learning system. Volumes were labelled as having or not having glaucomatous optic neuropathy according to the criteria of retinal nerve fibre layer thinning on reliable SDOCT images with position-correlated visual field defect. Heatmaps were generated for qualitative assessments.Findings6921 SDOCT volumes from 1 384 200 two-dimensional cross-sectional scans were studied. The 3D deep-learning system had an area under the receiver operation characteristics curve (AUROC) of 0·969 (95% CI 0·960–0·976), sensitivity of 89% (95% CI 83–93), specificity of 96% (92–99), and accuracy of 91% (89–93) in the primary validation, outperforming a two-dimensional deep-learning system that was trained on en face fundus images (AUROC 0·921 [0·905–0·937]; p<0·0001). The 3D deep-learning system performed similarly in the external validation datasets, with AUROCs of 0·893–0·897, sensitivities of 78–90%, specificities of 79–86%, and accuracies of 80–86%. The heatmaps of glaucomatous optic neuropathy showed that the learned features by the 3D deep-learning system used for detection of glaucomatous optic neuropathy were similar to those used by clinicians.InterpretationThe proposed 3D deep-learning system performed well in detection of glaucomatous optic neuropathy in both primary and external validations. Further prospective studies are needed to estimate the incremental cost-effectiveness of incorporation of an artificial intelligence-based model for glaucoma screening.FundingHong Kong Research Grants Council.
Targeting the therapy: Octreotide in thymoma relapse
Authors: G. Zampa
Journal: Journal of Clinical Oncology (2007)

18199 Background: Thymomas are rare slowly growing neoplasms, associated with myasthenia gravis, hypogammaglobulinemia and pure red-cell aplasia. About 40% of thymomas are invasive and some well encapsulated tumor recur years after surgical resection. 5 years survival rate in patients with noninvasive thymomas is 70 - 85% and decreases at 50 - 67% for invasive thymomas with the worst trend for stage IV (23%). Recurrence rate is 2% for stage I thymomas while for stage II and III is 28% and it decreases to 5% when thymectomy is followed by RT. Thymomas have a high content of somatostatin receptors and show high Indium-labeled octreotide ( 111 In-DTPA- D - Phe - octreotide) uptake when octrescan is performed. Methods: From 1997 to 2006 we treated 45 consecutive patients, age ranged from 19 to 84, with tymoma histological diagnosis. 12 patients had miastenia gravis, 1 SLE and 1 autoimmune pericarditis. In our series 36 pt performed toracotomy, 28 underwent chemotherapy and 23 underwent radioterapy. 25 patients (89%) chemotherapy treated showed stable disease at CT examination while 3 of 28(11%) cases who underwent chemotherapy showed progression disease. The chemotherapy schedule was PAC used both in neoadjuvant than in adjuvant setting. On the basis of positive octreotide uptake, after the patients’ informed consent had been obtained, we treated, 14 of 20 pt resulted scintigraphically positive, with octreotide (20 mg) every 2 weeks. Six of them refused treatment. Treatment was well tolerated and no side effects were reported.We monitored CgA and NSE. Results: At CT and Octreoscan examination, after octreotide treatment, 5 (35.7%) patients showed stable disease and also CgA and NSE decrease. In 2 (14.2%) cases we observed progression disease and in 4 (28,5%) cases partial response (decrease of mediastinic masses evaluated at previous CT examination). Conclusions: Treating thymoma recurrences or residual disease with octreotide seems to be feasible and safe. All pts treated showed good compliance. Positive scintillography gives the oncologist the possibility to address a new target, the somatostatin’s receptor, through the octreotide. No significant financial relationships to disclose.
Perfusion Assessment in Critical Limb Ischemia: Principles for Understanding and the Development of Evidence and Evaluation of Devices: A Scientific Statement From the American Heart Association
Authors: Sanjay Misra, Mehdi H. Shishehbor, Edwin A. Takahashi, Herbert D. Aronow, Luke P. Brewster, Matthew C. Bunte, Esther S.H. Kim, Jonathan R. Lindner, Kathleen Rich
Journal: Circulation (2019)

There are >12 million patients with peripheral artery disease in the United States. The most severe form of peripheral artery disease is critical limb ischemia (CLI). The diagnosis and management of CLI is often challenging. Ethnic differences in comorbidities and presentation of CLI exist. Compared with white patients, black and Hispanic patients have higher prevalence rates of diabetes mellitus and chronic renal disease and are more likely to present with gangrene, whereas white patients are more likely to present with ulcers and rest pain. A thorough evaluation of limb perfusion is important in the diagnosis of CLI because it can not only enable timely diagnosis but also reduce unnecessary invasive procedures in patients with adequate blood flow or among those with other causes for ulcers, including venous, neuropathic, or pressure changes. This scientific statement discusses the current tests and technologies for noninvasive assessment of limb perfusion, including the ankle-brachial index, toe-brachial index, and other perfusion technologies. In addition, limitations of the current technologies along with opportunities for improvement, research, and reducing disparities in health care for patients with CLI are discussed.
Inhibition of colon tumor metastasis in an orthotopic nude mouse model with the dual selective Src/Abl kinase inhibitor, AZD0530
Authors: K. Phillips, N. Parikh, T. Kuwai, T. Green, G. E. Gallick
Journal: Journal of Clinical Oncology (2007)

14032 Background: Colorectal cancer is the leading cause of cancer deaths in the USA, largely due to metastatic disease in the liver. The specific activity of the non-receptor protein tyrosine kinase, Src, is increased during colon tumor progression and contributes to metastasis; thus, Src inhibitors may have efficacy in the treatment of advanced-stage colon cancer. AZD0530 is a potent, orally available Src/Abl kinase inhibitor currently in clinical trials. Methods: We examined the effects of AZD0530 alone and in combination with oxaliplatin on two colon tumor cell lines, KM12L4 and LS174T in vitro and in orthotopic nude mouse models. AZD0530 inhibits in vitro proliferation and cellular migration of KM12L4 and LS174T, and decreases phosphorylation of the Src substrates FAK and paxillin in a dose- dependent manner. To examine the ability of AZD0530 to affect colon cancer growth and metastasis in a nude mouse model, we inoculated 1x10 6 cells into the cecum of nude mice. After 2 weeks, mice were treated with vehicle (n=12), AZD0530 alone (n=13; 25mg/kg/day by oral gavage), oxaliplatin alone (n=13; 5mg/kg/day twice weekly), or AZD0530 and oxaliplatin (n=13). Mice were sacrificed after 4 weeks of treatment. Results: Tumor incidence in all groups of mice was greater than 80%. Mice treated with AZD0530 had an average cecal tumor weight of 0.26 g compared with 0.32 g for control (P=0.24). In contrast, the incidence of liver metastases was reduced by 50% in mice treated with AZD0530 alone or oxaliplatin alone, and no mice developed pathologically evident liver metastases when the combination of inhibitors was used. Furthermore, in mice that developed liver metastases, AZD0530 decreased the size of these metastases 9-fold compared with control. Immunohistochemical analysis of primary cecal tumors demonstrated a decrease in phosphorylated Src (Y418) and FAK (Y861) in AZD0530-treated mice compared with control. Conclusions: These results support further investigation of AZD0530, both alone and in combination, as a new therapeutic strategy for the treatment of advanced colon cancer. No significant financial relationships to disclose.
Tuberculosis among asylum seekers in Milan, Italy: epidemiological analysis and evaluation of interventions
Authors: Simone Villa, Luigi Ruffo Codecasa, Marino Faccini, Mirella Maria Pontello, Maurizio Ferrarese, Paola Francesca Castellotti, Sabrina Senatore, Anna Lamberti, Ester Mazzola, Carlo Federico Perno, Daniela Campisi, Matteo Saporiti, Mario Carlo Raviglione
Journal: European Respiratory Journal (2019)

In countries of the European Union, tuberculosis (TB) mainly affects marginalised people, including asylum seekers. Migratory flows from high-incidence countries to Italy have increased up to 2017, posing challenges to the national health system. This study sought to assess TB and latent TB infection (LTBI) prevalence among asylum seekers in Milan during the biennium 2016-2017 and to evaluate interventions in place.A two-level active surveillance and screening system was developed for both TB and LTBI. Asylum seekers underwent an initial screening with a tuberculin skin test (TST) and a questionnaire at the receiving sites. At the Regional TB Reference Centre, those with a positive result underwent chest radiography. People aged <35 years with negative chest radiography results underwent further testing by interferon-γ release assay. If results of the assay were positive, LTBI treatment was offered. TB and LTBI prevalence were compared with literature data.A total of 5324 asylum seekers, mostly young (10-39 years; 98%), male (84%) and from sub-Saharan Africa (69%), were enrolled in the study. 69 active TB cases were diagnosed and 863 LTBI-positive individuals were detected. TB prevalence was high (1236 per 100 000 population) and LTBI prevalence was 28%. Despite losses (41%) during the transition from initial screening sites and the diagnostic centre, a good TB cure rate (84%) and optimal LTBI treatment completion (94%) were achieved.Our study shows that TB incidence is high among asylum seekers in Milan and that well-coordinated screening measures are critical for early diagnosis and treatment. It also proves that rolling out successful at-scale interventions for both prophylaxis and disease management is feasible.
Strong correlation between the rates of intrinsically antibiotic-resistant species and the rates of acquired resistance in Gram-negative species causing bacteraemia, EU/EEA, 2016
Authors: Vincent Jarlier, Liselotte Diaz Högberg, Ole E Heuer, José Campos, Tim Eckmanns, Christian G Giske, Hajo Grundmann, Alan P Johnson, Gunnar Kahlmeter, Jos Monen, Annalisa Pantosti, Gian Maria Rossolini, Nienke van de Sande-Bruinsma, Alkiviadis Vatopoulos, Dorota Żabicka, Helena Žemličková, Dominique L Monnet, Gunnar Skov Simonsen
Journal: Eurosurveillance (2019)

Background Antibiotic resistance, either intrinsic or acquired, is a major obstacle for treating bacterial infections. Aim Our objective was to compare the country-specific species distribution of the four Gram-negative species Escherichia coli , Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter species and the proportions of selected acquired resistance traits within these species. Method We used data reported for 2016 to the European Antimicrobial Resistance Surveillance Network (EARS-Net) by 30 countries in the European Union and European Economic Area. Results The country-specific species distribution varied considerably. While E. coli accounted for 31.9% to 81.0% (median: 69.0%) of all reported isolates, the two most common intrinsically resistant species P. aeruginosa and Acinetobacter spp. combined (PSEACI) accounted for 5.5% to 39.2% of isolates (median: 10.1%). Similarly, large national differences were noted for the percentages of acquired non-susceptibility to third-generation cephalosporins, carbapenems and fluoroquinolones. There was a strong positive rank correlation between the country-specific percentages of PSEACI and the percentages of non-susceptibility to the above antibiotics in all four species (rho &gt; 0.75 for 10 of the 11 pairs of variables tested). Conclusion Countries with the highest proportion of P. aeruginosa and Acinetobacter spp. were also those where the rates of acquired non-susceptibility in all four studied species were highest. The differences are probably related to national differences in antibiotic consumption and infection prevention and control routines.
Benefit-Risk Comparison in Patients with Immune Thrombocytopenia (ITP) Receiving Eltrombopag or Romiplostim: Real World Evidence (RWE) from 26 Hospital Institutions
Authors: Anna Forsythe, Anuja Roy, Menaka Bhor, Alex Allepuz, Maria Do Socorro Oliveira Portella, Christina Kwon, Gabriel Tremblay
Journal: Blood (2017)
Re: Baris Turkbey, Andrew B. Rosenkrantz, Masoom A. Haider, et al. Prostate Imaging Reporting and Data System Version 2.1: 2019 Update of Prostate Imaging Reporting and Data System Version 2. Eur Urol 2019;76:340–51
Authors: Byung Kwan Park
Journal: European Urology (2019)
Abstract 17063: The Potential Role of Sentinel Cerebral Protection System in Improving Outcomes of Transcatheter Aortic Valve Replacement Patients: A Meta-Analysis
Authors: Paul M Ndunda, Mohinder Vindhyal, Tabitha M Muutu, Sinan Khayyat, Sachin Srinivasan, Zaher Fanari
Journal: Circulation (2018)

Introduction: Stroke is still a major complication that is reported in 2-5% of patients at 30 days, after a transcatheter aortic valve replacement (TAVR). The Sentinel Cerebral Protection System (CPS) (Claret Medical Inc., Santa Rosa, CA. USA) is the only FDA approved cerebral embolic protection device (CEPD). This meta-analysis aims to assess the potential benefits of the routine use of CPS after TAVR. Methods: The Cochrane library, PubMed and Web of science were searched for relevant studies. Two authors independently screened and included studies that were randomized controlled trials or controlled observational studies comparing the use of Sentinel CPS with no CEPD in TAVR. Data was extracted and the risk of bias assessed using the Cochrane Collaboration tools (RoB2.0 and ROBINS-I). Results: Four studies (3 randomized controlled trials and 1 quasi experimental study) comparing 847 patients in whom sentinel CPS was used to 483 in whom it was not used. Two of the studies had low risk of bias and 2 had some concerns for risk of bias. The primary outcomes were the number or size of ischemic lesions on brain MRI in 2 studies, major cardiac and cerebrovascular events in 1 study and a composite of mortality or stroke in 1 study. Patients in whom Sentinel CPS was used had lower rates of 30-day clinical stroke (3.5% vs 6.1%; RR 0.51 [95% CI 0.29, 0.90] I 2 = 0%), 30-day mortality (0.8% vs 2.7%; RR 0.34 [95% CI 0.12, 0.92] I 2 = 0%) and major or life-threatening bleeding (3.3% vs 6.6%; RR 0.50 [95% CI 0.26, 0.98] I 2 = 16%). There was no significant difference between the two arms in the incidence of acute kidney injury (0.8% vs 1%; RR 0.85 [95% CI 0.22, 3.24] I 2 = 0%) and major vascular complications (5.1% vs 6%; RR 0.74 [95% CI 0.33, 1.67] I 2 = 45%). Conclusion: Sentinel CPS use in TAVR can be helpful in reducing the risk of stroke, mortality and major or life-threatening bleeding at 30 days.
Green tea polyphenols and its consituent epigallocatechin gallate inhibits proliferation of human breast cancer in vitro and in vivo
Authors: Rajesh L. Thangapazham, Anoop K. Singh, Jaya P. Gaddipati, Anuj Sharma, James Warren, Radha K. Maheshwari
Journal: Cancer Research (2005)

2292  Tea [Camellia sinensis (Theaceae)] intake is second only to water in terms of worldwide popularity as a beverage. Consumption of tea has been associated with many health benefits including the prevention of cancer and heart disease. Green tea is rich in polyphenols, which are antioxidants in nature, and antioxidants are found to be anti tumorogenic. In this study, we report the effectiveness of Green Tea Polyphenols (GTP) and its constituent Epigallocatechin Gallate (EGCG) in tumor regression using both in vitro and in vivo models. GTP and EGCG were found to be effective anti-proliferative agent by MTT assay. A significant increase in the G1 phase proportion in the cell cycle was found by flow cytometry after treatment with GTP and EGCG. Western blot analysis for cell cycle proteins corroborates the G1 block. Quantitative Fluorescence labeling resulted in demonstrating a 24-28 % reduction in the invasion through matrigel by EGCG and 15-23 % reduction by GTP in a dose dependent fashion. Furthermore, using MDA-MB-231 human breast carcinoma xenograft in athymic nude mice, we have shown that GTP and EGCG are capable of delaying the tumor incidence as well as reducing the tumor burden in vivo. Our results indicate that both GTP and EGCG are potent inhibitor of cell proliferation both in vitro and in vivo and have the ability to decrease the invasive property of the highly metastatic MDA-MB-231. All together, these data sustain our contention that Green Tea Polyphenol and EGCG have anti-tumor properties.