tbuckley/cabot-search huggingface dataset:
Study of copy number variations of OCT4 and SOX2 pluripotency genes in stomach tumors.
Authors: Vladimir Sez Trifanov, Tanzila Beksultanovna Kazieva, Konstantin Vladimirovich Dvadnenko, Martin Zamirovich Tatimov, Alexander V. Snezhko, Sergey Vladimirovich Sanamyanc, Nikolai Borisovich Chizhikov, Oleg Ivanovich Kit
Journal: Journal of Clinical Oncology (2015)

e15095 Background: In spite of widespread reduction in the incidence of stomach cancer, more than 1 million people develop it all over the world. Since mortality from this disease is getting close to morbidity, study of pathogenesis of stomach cancer is an urgent task of oncology. Copy number variation (CNV) is one of the fundamental mechanisms of changes in the expression of oncogenes and tumor suppressor genes in oncotransformation. The purpose of the study was to analyze variations in copy number of the OCT4 and SOX2 genetic loci in tumoral and conditionally healthy stomach tissues. Methods: Stomach tumor tissues of 29 patients with adenocarcinoma, signet ring cell carcinoma and synchronous cancer (adenocarcinoma+signet ring cell carcinoma) were studied. Genomic DNA was extracted with phenol-chloroform method after pathological verification of archival paraffin blocks. Primers were designed using OCT4, SOX2 and B2M reference DNA sequences of NCBI GenBank. RT-qPCR was conducted using thermocycler Bio-Rad CFX96 (Bio-Rad, USA). Locus B2M was used as a reference. Statistical analysis was performed using Microsoft Excel 2013 and Statistica 8.0. The differences were assessed with Mann-Whitney U-test for p < 0.05. Results: Patients with G1, G2 adenocarcinoma showed significant decline in the copy number of OCT4 and SOX2 genes by 41% and 32%, G3 – by 73.5% and 77.4%, respectively. Significant variations in OCT4 and SOX2 copy number in signet ring cell carcinoma were not found. Tendency towards SOX2 amplification was observed in synchronous cancer, as well as absence of OCT4 CNV in comparison with conditionally healthy stomach tissue. Conclusions: The results show an intense mutation process in the OCT4 and SOX2 genetic loci and similar CNV of these genes in the studied histological types of cancer. Study of cancerogenesis mechanisms is necessary for development of new therapeutic approaches and search for potential molecular markers available for early diagnostics and prognosis of the disease.
Coping and Prognostic Awareness in Patients With Advanced Cancer
Authors: Ryan D. Nipp, Joseph A. Greer, Areej El-Jawahri, Samantha M. Moran, Lara Traeger, Jamie M. Jacobs, Juliet C. Jacobsen, Emily R. Gallagher, Elyse R. Park, David P. Ryan, Vicki A. Jackson, William F. Pirl, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2017)

Purpose Patients' understanding of their illness is key for making informed treatment decisions, yet studies suggest an association between prognostic awareness and worse quality of life (QOL) and mood among patients with advanced cancer. We sought to explore the relationships among prognostic awareness, coping, QOL, and mood in patients with newly diagnosed, incurable cancer. Methods We assessed patients' self-reported health status and treatment goal (Prognosis and Treatment Perceptions Questionnaire), coping (Brief COPE), QOL (Functional Assessment of Cancer Therapy-General), and mood (Hospital Anxiety and Depression Scale) within 8 weeks of incurable lung or GI cancer diagnosis. We used linear regression to examine associations and interaction effects among patients' health status and treatment goal, coping strategies, QOL, and mood. Results Patients who reported a terminally ill health status had worse QOL (unstandardized coefficient [B] = -6.88; P < .001), depression (B = 1.60; P < .001), and anxiety (B = 1.17; P = .007). Patients who reported their oncologist's treatment goal was "to cure my cancer" had better QOL (B = 4.33; P = .03) and less anxiety (B = -1.39; P = .007). We observed interaction effects between self-reported health status and treatment goal and certain coping strategies. Specifically, subgroup analyses showed that greater use of positive reframing was related to better QOL (B = 2.61; P < .001) and less depression (B = -0.78; P < .001) among patients who reported a terminally ill health status. Active coping was associated with better QOL (B = 3.50; P < .001) and less depression (B = -1.01; P < .001) among patients who acknowledged their oncologist's treatment goal was not "to cure my cancer." Conclusion Prognostic awareness is related to worse QOL and mood in patients with newly diagnosed, incurable cancer; however, the use of certain coping strategies may buffer these relationships. Interventions to improve patients' prognostic awareness should seek to cultivate more adaptive coping strategies in order to enhance QOL and mood.
Recurrent deep vein thrombosis with a protein S Tokushima mutation
Authors: R. Torai, T. Makino, M. Mizawa, M. Hayashi, F. Furukawa, H. Niimi, T. Shimizu
Journal: British Journal of Dermatology (2017)

Deep vein thrombosis (DVT) is multifactorial disease caused by acquired risk factors such as bed rest, surgery and malignancies as well as genetic factors. Regarding the genetic factors, factor V Leiden (c.1601G>A, p.R534Q) and the prothrombin G20210A mutations are well-known risk factors for DVT in Caucasians.1 However, these two mutations do not exist in Japanese populations. A missense mutation (c.586A>G, p. K196E) in protein S gene, known as the protein S (PS) Tokushima mutation, was identified as a genetic risk factor for DVT in Japanese populations.2 We herein report a young Japanese patient with recurrent DVT in whom a PS Tokushima mutation was detected.

This article is protected by copyright. All rights reserved.
Follicular lymphoma in young patients (>50 yrs): A population-based analysis of the Danish lymphoma registry
Authors: Francesco d Amore, Peter De Nully Brown, Lars Møller Pedersen, Bjarne Bach Pedersen, Michael Pedersen, Ole Vestergaard Gadeberg, Anne Bukh, Mads Hansen, Stanislaw Pulczynski, Steen Ingeberg, Torben Mouritz Andersen, Mikael Frederiksen, Michael Boe Møller, Leif Spange Mortensen
Journal: Annals of Oncology (2008)
Modulation of T Cell Compartment in a Preclinical CLL Murine Model By a Selective PI3K Delta Inhibitor, TGR-1202
Authors: Kamira Karen Maharaj, John J. Powers, Mibel Pabon-Saldana, Renee Fonseca, Alex Achille, Susan Deng, Hari P. Miskin, Dave Maryanski, Eva Sahakian, Javier Pinilla-Ibarz
Journal: Blood (2016)
Immunotherapy for Breast Cancer: What Are We Missing?
Authors: Robert H. Vonderheide, Susan M. Domchek, Amy S. Clark
Journal: Clinical Cancer Research (2017)

Abstract The recent demonstration of modest single-agent activity of programmed death-ligand 1 (PD-L1) and programmed death receptor-1 (PD-1) antibodies in patients with breast cancer has generated hope that breast cancer can be made amenable to immunotherapy. Depending on the subtype of breast cancer, it is now clear in both primary and metastatic disease that the extent of tumor-infiltrating T cells is not only prognostic for survival but predictive of response to nonimmune, standard therapies. Despite these findings, immune cytolytic activity in spontaneous breast tumors, the burden of nonsynonymous tumor mutations, and the predicted load of neoepitopes—factors linked to response to checkpoint blockade in other malignancies—are all relatively modest in breast cancer compared with melanoma or lung cancer. Thus, in breast cancer, combinations of immune agents with nonredundant mechanisms of action are high-priority strategies. For most breast cancers that exhibit relatively modest T-cell infiltration, major challenges include immune suppression in the tumor microenvironment as well as failed or suboptimal T-cell priming. Agents that trigger de novo T-cell responses may be critical for the successful development of cancer immunotherapy and immune prevention in breast cancer. Success may also require reaching beyond nonsynonymous mutations as the T-cell epitopes to target, especially as numerous unmutated proteins were validated as breast cancer–associated antigens in the pre-checkpoint era. A deeper understanding of the immunobiology of breast cancer will be critical for immunotherapy to become broadly relevant in this disease. Clin Cancer Res; 23(11); 2640–6. ©2017 AACR. See all articles in this CCR Focus section, “Breast Cancer Research: From Base Pairs to Populations.”
Determination of activity of endotoxin gram-negative microorganisms in the diagnostics of sepsis in cancer patients.
Authors: Alexey N. Shevchenko, Natalya Dmitrievna Ushakova, Maxim V. Chetverikov, Elena Yurievna Zlatnik, Tatyana A. Zykova, Olga A. Bogomolova
Journal: Journal of Clinical Oncology (2014)

e14017 Background: The purpose of the study was to analyze the role of EAA -test in the diagnostics and and evaluation of the effectiveness of intensive treatment of septic complications in cancer patients. Methods: We examined 45 cancer patients with postoperative period affected by the development of septic process. Clinical and laboratory signs of sepsis were identified in all cases. The severity of the condition measured on the APACHE-II scale was over 16, SAPS II - 20, SOFA - 7, MODS - 6 points. The level of activity of endotoxin in EAA -test was from 0,46 up to 1.37. On the 3-5th day from the start of standard conservative intensive treatment (detoxification, infusion-transfusion, antibacterial, syndromic therapy) EAA-test index of 19 pts decreased to 0.30-0,41 which correlated with positive dynamics of clinical and laboratory picture of generalized inflammation process. Progression of the clinical and laboratory signs of multiorgan failure was observed in 33 pts, EAA-test indices remained high from 0.65 to 0.83. Results: After inclusion of methods of extracorporal detoxication (hemo/hemodiafiltration, selective LPS-adsorption) in the intensive treatment complex on indications, regress of intensity of clinical manifestations of generalized inflammation was recorded in 22 of 33 patients (66,7%) with simultaneous reducing of endotoxin activity level. In 11 cases, EAA– test indices remained high or rising. An unfavorable course of the disease was registered in all these cases, 9 of 11 pts died. Conclusions: The findings show the adequacy of determination of endotoxin activity level by EAA-test in diagnostics of septic complication process, prognosis of generalized inflammation process and planning of an intensive therapeutic approach.
Abstract P017: Plasmonic Photothermal Therapy of Atherosclerosis with the Use of Silica-Gold Nanoparticles and Mesenchymal Stem Cells Versus Ferromagnetic Approach
Authors: Alexander Kharlamov, Alexander Perrish, Jan Gabinsky, Eugene Ivanova
Journal: Circulation Research (2011)

Background. Some modern angioplasty techniques generally just manipulate the form of the plaque and have some clinical and technical restrictions, relatively high complication rate and restenosis risk. Methods. A total of 101 Yucatan miniature swines were assigned to the three groups (34 pigs into 60/15–70/40 nm silica-gold nanoparticles (NPs) nanogroup, 34 swines - into ferro-magnetic group with 100 nm NPs with delivery in hand of magnetic fields, and 33 - in sirolimus stenting control). Animals in nanogroup were split up to 4 subsets by delivery approach: 1) infused circulating progenitor cells; 2) with infused ultrasound-mediated albumin-coated gas-filled microbubbles; 3) CD73+CD105+ progenitor cells in the composition of bioengineered on-artery patch; 4) CD73+CD105+ progenitor cells transplanted by manual subadventitial injection. Results. A change of the PV (mm3) immediately after the laser irradiation/ in 6 months in groups were −28.9/ −56.8%, −30.8/ −59.1% and 0/ +4.3% (p&lt;0.01) respectively, and in the subsets in 6 mns reached −54.5/ −45.9/ −74.7/ −61.8% (p&lt;0.05) respectively. Some cases of atherothrombosis (3 cases in S2 subset) and distal embolism (8/34, 23.5% in nanogroup, 2/33, 6% in control) were revealed while first 4 weeks. Restenosis confirmed in 3 (9%) swines of stenting group only. An impact over the non-organic part of the plaque was predominated in nanogroup (−43.4% vs −12.1% and +3.7% respectively, p&lt;0.005). Coronary flow-mediated vasodilation was observed after hyperemia and injection of nitroglycerine (+10.2 and +16.6%, +8.2 and +9.6%, +8.1 and +9.8% in groups respectively, p&lt;0.05). The highest level of the infiltration with NPs was achieved in the liver that equal to 612 units per cm3 without signs of fibrosis or allergic responses. There were 344, 201 and 99 units per cm3 in the heart, brain, and lungs respectively without any morphological dynamics. Conclusion. Nanoburning is the novel promising technique to demolish and melt the plaque especially in combination with stem cell technologies challenging functional restoration of the vessel. Plasmonics is the high-effective and safe alternative to stenting for angioplasty.
Translational Genomics: Practical Applications of the Genomic Revolution in Breast Cancer
Authors: Lucy R. Yates, Christine Desmedt
Journal: Clinical Cancer Research (2017)

The genomic revolution has fundamentally changed our perception of breast cancer. It is now apparent from DNA-based massively parallel sequencing data that at the genomic level, every breast cancer is unique and shaped by the mutational processes to which it was exposed during its lifetime. More than 90 breast cancer driver genes have been identified as recurrently mutated, and many occur at low frequency across the breast cancer population. Certain cancer genes are associated with traditionally defined histologic subtypes, but genomic intertumoral heterogeneity exists even between cancers that appear the same under the microscope. Most breast cancers contain subclonal populations, many of which harbor driver alterations, and subclonal structure is typically remodeled over time, across metastasis and as a consequence of treatment interventions. Genomics is deepening our understanding of breast cancer biology, contributing to an accelerated phase of targeted drug development and providing insights into resistance mechanisms. Genomics is also providing tools necessary to deliver personalized cancer medicine, but a number of challenges must still be addressed. Clin Cancer Res; 23(11); 2630-9. ©2017 AACRSee all articles in this CCR Focus section, "Breast Cancer Research: From Base Pairs to Populations."
Is it time to stop using percutaneous transhepatic biliary drainage?
Authors: Ryan Law, Manuel Perez-Miranda
Journal: Endoscopy (2017)

See also: Conversion of external percutaneous transhepatic biliary drainage to endoscopic ultrasound-guided hepaticogastrostomy after failed standard internal stenting for malignant biliary obstruction Endoscopy eFirstDOI: 10.1055/s-0043-102388
Characterization of Clinical Cases of Advanced Papillary Renal Cell Carcinoma via Comprehensive Genomic Profiling
Authors: Sumanta K. Pal, Siraj M. Ali, Evgeny Yakirevich, Daniel M. Geynisman, Jose A. Karam, Julia A. Elvin, Garrett M. Frampton, Xuan Huang, Douglas I. Lin, Mark Rosenzweig, Doron Lipson, Philip J. Stephens, Jeffrey S. Ross, Vincent A. Miller, Neeraj Agarwal, Brian Shuch, Toni K. Choueiri, Jon H. Chung
Journal: European Urology (2017)
Estrogen Replacement Reduces Risk and Increases Survival Times of Women With Hepatocellular Carcinoma
Authors: Manal M. Hassan, Gehan Botrus, Reham Abdel-Wahab, Robert A. Wolff, Donghui Li, David Tweardy, Alexandria T. Phan, Ernest Hawk, Milind Javle, Ju-Seog Lee, Harrys A. Torres, Asif Rashid, Renato Lenzi, Hesham M. Hassabo, Yasmin Abaza, Ahmed S. Shalaby, Sahin Lacin, Jeffrey Morris, Yehuda Z. Patt, Christopher I. Amos, Saira A. Khaderi, John A. Goss, Prasun K. Jalal, Ahmed O. Kaseb
Journal: Clinical Gastroenterology and Hepatology (2017)
Abstract 236: Cardiac Overexpression of Thioredoxin-1 Delays Mitochondrial Damage and Prolongs Survival in Septic Mice
Authors: Juana P Sanchez-Villamil, Veronica D’Annunzio, Ines Rebagliati, Paola Finocchietto, Jorge Peralta, Celina Morales, Ricardo J Gelpi, Juan J Poderoso, Maria C Carreras
Journal: Circulation Research (2015)

Introduction: Current evidence suggests a main role of thioredoxin-1 (trx1) in the protection against oxidative stress. However, it is unknown yet a putative role of trx1 in the regulation of contractility and mitochondrial function, dynamics and biogenesis in sepsis-induced myocardial dysfunction in which oxidative stress is an underlying cause. Methods: Transgenic male mice (Tg-trx1) and its wildtype (wt) were subjected to cecal ligation and double puncture or sham operation. After 6, 18 and 24 h, antioxidant enzymes, protein carbonylation and mitocondrial function were evaluated. Hearts were isolated and perfused using the Langendorff technique. Inotropism was evaluated through left ventricular developed pressure (LVDP) and contractile reserve after β-adrenergic stimulus by addition of isoproterenol (ISO) (1 μM). Evaluation of mitochondrial fusion-fission dynamics (Drp1, Mfn2, Opa1) and biogenesis (PGC-1α, NRF-1 and TFAM) were made by real-time qPCR. Results: Over the time course of sepsis, there was an improvement in average life expectancy in Tg-trx1 (Tg-trx1: 36, wt: 28 h; p=0.0204), and 15 percentages points higher β -adrenergic response at 6 h compared to wt (22.8 vs 7.8%, means of relative percentage differences respectively). Inhibition of complex I activity, protein oxidation, and loss of membrane potential was lower in Tg-trx1, with a sustained MnSOD activity at 24 h. mRNA levels of Opa1 were significantly reduced in sepsis, accompanied by ultrastructural alterations in mitochondrial cristae, while significant Drp1 activation (measured by Ser P616 phosphorylation) was observed in wt mice at 24 h. PGC-1 α mRNA decreased at 6 h in both groups, and then, showed a 2.5-fold increase in Tg-trx1 at 24 h. Autophagy was demonstrated by increased LC3-II/LC3-I ratios in both groups during the progression of sepsis, although the levels were early higher in Tg-Trx1. No indicators of apoptosis were observed. Conclusions: The results show that mice with cardiac-specific overexpression of Trx1 have higher survival. Trx1 provides protection against oxidative stress, which seems to preserve contractile reserve and keep mitochondrial biogenesis. Associated with mitochondrial autophagy-processes allow mitochondrial renewal and life extension.
Sarcomatoid carcinoma of the prostate: A case series from Johns Hopkins Hospital.
Authors: Mark Christopher Markowski, Mario A. Eisenberger, Marianna Zahurak, Jonathan I Epstein, Channing Judith Paller
Journal: Journal of Clinical Oncology (2015)

e16105 Background: Sarcomatoid prostate cancer is a rare malignancy representing < 1% of all prostate neoplasms and is associated with poor clinical outcomes. Limited data is available regarding survival based on stage and treatment options. Methods: We reviewed the clinical outcomes of patients with a pathologically confirmed diagnosis of sarcomatoid prostate cancer. The primary statistical objective was to estimate overall survival (OS) and assess the survival of patients at different stages treated with either local and/or systemic approaches. Results: We identified 70 transurethral resections, needle biopsies or prostatectomy specimens that were reviewed by the Department of Pathology at Johns Hopkins Hospital from 2002-2012 and given the diagnosis of sarcomatoid prostate cancer. Of the 45 patients with available survival data, complete medical histories were obtained on 27 patients who were stratified based on a modified staging system (local disease, local disease with bladder invasion, and metastatic disease). After a median follow-up of 106 months, the median overall survival (OS) of patients in the local disease group was not reached. Notably, five of the nine patients diagnosed with local disease survived > 5 years and were treated with surgery and/or external beam radiation therapy. The OS hazard was significantly increased in patients with either clinical evidence of bladder invasion (HR: 20.46 [95% CI: 2.43,172]; p = < 0.0001) or metastatic disease (HR: 43.34 [95% CI: 4.39,427.4]; p = < 0.0001), which both demonstrated poor outcomes (median OS: local with bladder invasion – 9 months; metastatic disease – 7.1 months). Four patients with advanced disease were treated with androgen deprivation therapy (ADT) and no PSA response was observed. Multiple chemotherapy regimens were used including docetaxel. Two of the five patients who received docetaxel had PSA and partial radiographic responses lasting 5 and 8 months. Conclusions: This retrospective analysis suggests that local sarcomatoid prostate cancer can be effectively treated with definitive therapy leading to favorable outcomes. More advanced disease confers a poor prognosis of rapid progression and short survival with no clear effective treatment.
Clinical validation of the 7th AJCC-TNM nodal staging system in lymph node-positive patients undergoing radical cystectomy.
Authors: Eila C. Skinner, Harman Maxim Bruins, Ryan Paul Dorin, Barbara Rubino, Gus Miranda, Jie Cai, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2012)

4588 Background: The AJCC TNM staging system for bladder cancer has recently been updated. In the new 7 th edition, staging of lymph node (LN) metastases is based on anatomical location instead of size as in the former 6 th edition. This study evaluated whether the prognostic value of nodal staging according to the 7 th edition is superior to the 6 th edition. Methods: Prospectively collected data of patients who underwent radical cystectomy (RC) at a high-volume center between 2002 and 2008 were reviewed. Patients who underwent RC for non-urothelial cancer, received neo-adjuvant therapy or had non-LN metastatic disease at the time of RC were excluded. All patients underwent RC with extended lymphadenectomy up to the inferior mesenteric artery. LNs were submitted in predesignated anatomically defined packets. Detailed data on the number, size and location of LN metastases were recorded. Both the 6 th and 7 th edition AJCC TNM editions were used to stage LN positive (LN+) disease. Median follow-up time was 2.8 years. Kaplan-Meier analysis was used to estimate overall survival (OS) and recurrence-free survival (RFS). Results: A total of 637 patients were identified of whom 141 patients (22.1%) had LN+ disease. In total, 83 patients (58.9%) received adjuvant chemotherapy. Administration of adjuvant chemotherapy did not differ significantly per N-stage according to both editions. Based on the 6 th edition, 31 patients (22.0%) had N1 disease, 105 patients (74.5%) N2 disease and 5 patients (3.5%) N3 disease. Three-year RFS rates for N1, N2 and N3 disease were 51%, 43% and 0% respectively (p = 0.87). Based on the 7 th edition, 29 patients (20.6%) had N1 disease, 60 patients (42.6%) N2 disease and 52 patients (36.9%) N3 disease. Three-year RFS rates for N1, N2 and N3 disease were 51%, 42% and 45%, respectively (p = 0.84). Conclusions: Neither the AJCC-TNM 7 th edition (location-based) LN staging nor the 6 th edition (size-based) staging performed well as a prognostic tool for the patients in this cohort. The new staging system moved a large percent of patients into the N3 category, which did not have a worse prognosis than either the N1 or N2 categories. A better staging system for LN+ bladder cancer patients needs to be developed.