tbuckley/cabot-search huggingface dataset:
Surgical outcomes and implications for cure in active surveillance patients who undergo delayed radical prostatectomy.
Authors: B. J. Trock, Z. Feng, P. Landis, J. I. Epstein, B. Carter
Journal: Journal of Clinical Oncology (2010)

4506 Background: Active surveillance (AS) with delayed treatment is an option for men thought to harbor low-risk prostate cancer. This delay is not thought to compromise likelihood of cure, but surgical pathology outcomes for such men have only been evaluated in small series. We compared surgical pathology outcomes in an AS cohort who underwent delayed radical prostatectomy (RP) vs. a group of men eligible for AS but who instead chose immediate RP. Methods: Since 1995, 772 men have enrolled in the AS program. Eligible men must have biopsy Gleason ≤6, ≤2 positive cores, ≤50% involvement of any core with cancer, and PSA density <0.15. They are re-biopsied annually; any increase in the above biopsy parameters triggers a recommendation for treatment. 116 (15%) men underwent RP at a median of 2 (0.5-8) years after diagnosis. They were matched to 348 men who met the above eligibility criteria for AS but who chose to have immediate RP. Results: At surgery, men initially managed with AS were significantly more likely to have non-organ-confined tumor (p=0.009) and high-grade tumor (Gleason score ≥ 3+4; p=0.0001) than matched immediate RP men. However, when we excluded 43 AS patients upgraded to Gleason ≥7 at a follow-up biopsy, the remaining AS patients had surgical pathology outcomes similar to immediate RP patients (Table). Considering the entire AS cohort of 772, the risk of high-grade tumor at follow-up biopsy or RP was 7.3% per year of follow-up. Conclusions: In the largest cohort to date, AS patients who undergo delayed RP in the absence of biopsy grade progression have similar risk of adverse pathology as matched men who undergo immediate RP. The message to men considering AS must balance the overall low rate of adverse pathology with the knowledge that a small fraction of men upgraded at biopsy will have a potentially noncurable tumor. RP pathology All AS (n=110) AS with biopsy Gleason always ≤6 (n=67) Matched immediate RP (n=348) p value* Pathologic stage: 0.009, 0.316 Organ confined 73% 77% 85% EPE 22% 23% 14% SVI 3% 0% 1% LN metastases 2% 0% 0.3% Post-RP Gleason: 0.0001, 0.747 ≤ 6 56% 75% 74% 3+4 22% 16% 19% ≥ 3+4 22% 9% 7% * First p value compares All AS vs. Immediate RP; second p value compares AS with biopsy Gleason always ≤6 vs. Immediate RP. No significant financial relationships to disclose.
Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice
Authors: Ningwen Tai, Jian Peng, Fuqiang Liu, Elke Gulden, Youjia Hu, Xiaojun Zhang, Li Chen, F. Susan Wong, Li Wen
Journal: The Journal of Experimental Medicine (2016)

Both animal model and human studies indicate that commensal bacteria may modify type 1 diabetes (T1D) development. However, the underlying mechanisms by which gut microbes could trigger or protect from diabetes are not fully understood, especially the interaction of commensal bacteria with pathogenic CD8 T cells. In this study, using islet-specific glucose-6-phosphatase catalytic subunit–related protein (IGRP)–reactive CD8 T cell receptor NY8.3 transgenic nonobese diabetic mice, we demonstrated that MyD88 strongly modulates CD8+ T cell–mediated T1D development via the gut microbiota. Some microbial protein peptides share significant homology with IGRP. Both the microbial peptide mimic of Fusobacteria and the bacteria directly activate IGRP-specific NY8.3 T cells and promote diabetes development. Thus, we provide evidence of molecular mimicry between microbial antigens and an islet autoantigen and a novel mechanism by which the diabetogenicity of CD8+ T cells can be regulated by innate immunity and the gut microbiota.
Dietary fat drives whole-body insulin resistance and promotes intestinal inflammation independent of body weight gain
Authors: Benjamin A.H. Jensen, Thomas S. Nielsen, Andreas M. Fritzen, Jacob B. Holm, Even Fjære, Annette K. Serup, Kamil Borkowski, Steve Risis, Simone I. Pærregaard, Ida Søgaard, Audrey Poupeau, Michelle Poulsen, Tao Ma, Christian Sina, Bente Kiens, Lise Madsen, Karsten Kristiansen, Jonas T. Treebak
Journal: Metabolism (2016)

BackgroundThe obesogenic potential of high-fat diets (HFD) in rodents is attenuated when the protein:carbohydrate ratio is increased. However, it is not known if intake of an HFD irrespective of the protein:carbohydrate ratio and in the absence of weight gain, affects glucose homeostasis and the gut microbiota.MethodsWe fed C57BL6/J mice 3 different HFDs with decreasing protein:carbohydrate ratios for 8 weeks and compared the results to a LFD reference group. We analyzed the gut microbiota composition by 16S rDNA amplicon sequencing and the intestinal gene expression by real-time PCR. Whole body glucose homeostasis was evaluated by insulin and glucose tolerance tests as well as by a hyperinsulinemic euglycemic clamp experiment.ResultsCompared with LFD-fed reference mice, HFD-fed mice, irrespective of protein:carbohydrate ratio, exhibited impaired glucose tolerance, whereas no differences were observed during insulin tolerance tests. The hyperinsulinemic euglycemic clamp revealed tissue-specific effects on glucose homeostasis in all HFD-fed groups. HFD-fed mice exhibited decreased insulin-stimulated glucose uptake in white but not in brown adipose tissue, and sustained endogenous glucose production under insulin-stimulated conditions. We observed no impairment of insulin-stimulated glucose uptake in skeletal muscles of different fiber type composition. HFD-feeding altered the gut microbiota composition paralleled by increased expression of pro-inflammatory cytokines and genes involved in gluconeogenesis in intestinal epithelial cells of the jejunum.ConclusionsIntake of a HFD profoundly affected glucose homeostasis, gut inflammatory responses, and gut microbiota composition in the absence of fat mass accretion.
Comparison of resilience scores of an ambulatory nonselected population of cancer patients older than age 70 or younger than age 50 receiving chemotherapy treatment.
Authors: O. C. Junior, A. F. Ferreira Filho, M. A. de Souza, A. P. Wunder, I. M. Tavares Cavalcante, D. L. Da Silva
Journal: Journal of Clinical Oncology (2010)

e19657 Background: In psychology, resilience is the hability of people to cope with stressors and maintain psychological balance and adaptation despite negative life circumstances. Scanty data exists regarding resilience quantification in the population of elderly cancer patients. The objective of this study is to gain insight of eventual differences in resilience scores (RS) between older and younger patients undergoing ambulatory chemotherapy treatment of cancer. Methods: Individual RS were measured by the Wagnild and Young Scale, validated for portuguese language from Brazil. Possible scores range from 25 to 175 with higher scores reflecting higher resilience. During the years 2008 - 2009, this scale was applied by oncology nurses to 99 non-selected ambulatory cancer patients during chemotherapy treatment at Oncosinos/Hospital Regina in Novo Hamburgo, and Pronutrir/ Hospital São Mateus in Fortaleza-Brazil. The study was approved by the Ethics Comitte and all patiens signed the informed consent form. Results: We analysed a total of 48 patients with either < 50 years (24 patients) or > 70 years (24 patients). The mean age was 42±7 years in the younger group (range 19-49) and 75±3 (range 71-82) in older patients. The most common cancer types in both groups were: breast (16), colon (10) and lung (7). Older patients had stage IV disease more frequently when compared to younger patients (66% versus 33%), although this finding did not reach statistical significance, (P= 0.12). The group of patients with > 70 years had chemotherapy treatment with palliative intention more frequently (17/24) when compared to younger patients (10/24), (P= 0.058). There was no statistical difference between the total resilience score of older patients (142 ± 25), as compared to that of younger patients (138± 12), (P=0.13). Conclusions: Despite the more frequent presence of stage IV cancer and administration of chemotherapy with palliative intention in patients with > 70 years, our series did not demonstrated any statistical difference in RS between older and younger patients. To confirm and fully explain these findings, further research on relience of elderly patients with cancer is still needed. No significant financial relationships to disclose.
Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy
Authors: Boyan Fang, Andrew McKeon, Shannon R. Hinson, Thomas J. Kryzer, Sean J. Pittock, Allen J. Aksamit, Vanda A. Lennon
Journal: JAMA Neurology (2016)

<h3>Importance</h3> A novel astrocytic autoantibody has been identified as a biomarker of a relapsing autoimmune meningoencephalomyelitis that is immunotherapy responsive. Seropositivity distinguishes autoimmune glial fibrillary acidic protein (GFAP) meningoencephalomyelitis from disorders commonly considered in the differential diagnosis. <h3>Objective</h3> To describe a novel IgG autoantibody found in serum or cerebrospinal fluid that is specific for a cytosolic intermediate filament protein of astrocytes. <h3>Design, Setting, and Participants</h3> Retrospective review of the medical records of seropositive patients identified in the Mayo Clinic Neuroimmunology Laboratory from October 15, 1998, to April 1, 2016, in blinded comprehensive serologic evaluation for autoantibody profiles to aid the diagnosis of neurologic autoimmunity (and predict cancer likelihood). <h3>Main Outcomes and Measures</h3> Frequency and definition of novel autoantibody, the autoantigen's immunochemical identification, clinical and magnetic resonance imaging correlations of the autoantibody, and immunotherapy responsiveness. <h3>Results</h3> Of 103 patients whose medical records were available for review, the 16 initial patients identified as seropositive were the subject of this study. Median age at neurologic symptom onset was 42 years (range, 21-73 years); there was no sex predominance. The novel neural autoantibody, which we discovered to be GFAP-specific, is disease spectrum restricted but not rare (frequency equivalent to Purkinje cell antibody type 1 [anti-Yo]). Its filamentous pial, subventricular, and perivascular immunostaining pattern on mouse tissue resembles the characteristic magnetic resonance imaging findings of linear perivascular enhancement in patients. Prominent clinical manifestations are headache, subacute encephalopathy, optic papillitis, inflammatory myelitis, postural tremor, and cerebellar ataxia. Cerebrospinal fluid was inflammatory in 13 of 14 patients (93%) with data available. Neoplasia was diagnosed within 3 years of neurologic onset in 6 of 16 patients (38%): prostate and gastroesophageal adenocarcinomas, myeloma, melanoma, colonic carcinoid, parotid pleomorphic adenoma, and teratoma. Neurologic improvement followed treatment with high-dose corticosteroids, with a tendency of patients to relapse without long-term immunosuppression. <h3>Conclusions and Relevance</h3> Glial fibrillary acidic protein–specific IgG identifies a distinctive, corticosteroid-responsive, sometimes paraneoplastic autoimmune meningoencephalomyelitis. It has a lethal canine equivalent: necrotizing meningoencephalitis. Expression of GFAP has been reported in some of the tumor types identified in paraneoplastic cases. Glial fibrillary acidic protein peptide–specific cytotoxic CD8<sup>+</sup>T cells are implicated as effectors in a transgenic mouse model of autoimmune GFAP meningoencephalitis.
A6-01: Immune tolerance of cancer is mediated by IDO which is inhibited by COX-2 inhibitor through Treg cells
Authors: Sung Yong Lee, Jin Yong Jung, Kyoung Ju Lee, Eun Joo Lee, Ki Hwan Jung, Je Hyeong Kim, Chol Shin, Jae Jeong Shim, Kwang Ho In, Kyung Ho Kang, Se Hwa Yoo
Journal: Journal of Thoracic Oncology (2007)
Long-term survival of non-small cell lung cancer (nsclc) patients with single station n2 disease treated with concurrent chemoradiotherapy
Authors: Bart Reymen, Angela Van Baardwijk, Rinus Wanders, Jacques Borger, Ruud Houben, Anne-Marie C Dingemans, Gerben Bootsma, Cordula Pitz, Ragnar Lunde, Philippe Lambin, Dirk De Ruysscher
Journal: Journal of Thoracic Oncology (2011)
P1-037: Epidemiological study of lung cancer in western Mexico
Authors: Carmen M. Gurrola-Diaz, Ana E. Gonzalez-Santiago, Jessica Gonzalez-Valencia, Paola G. Santillan-Loza, Teresita Plascencia-Ortiz, Luz A. Mendoza-Topete, Rogelio Troyo-Sanroman
Journal: Journal of Thoracic Oncology (2007)
Tolerability and Efficacy of Treatments in Elderly Patients with Hodgkin Lymphoma: A Report from the Nebraska Lymphoma Study Group
Authors: Roberto A. Ferro, Vijaya R. Bhatt, Martin Bast, Lynette Smith, R. Gregory Bociek, Matthew A. Lunning, Philip J Bierman, Julie M. Vose, James O. Armitage
Journal: Blood (2015)
Identification of Interferon-Stimulated Genes with Antiretroviral Activity
Authors: Melissa Kane, Trinity M. Zang, Suzannah J. Rihn, Fengwen Zhang, Tonya Kueck, Mudathir Alim, John Schoggins, Charles M. Rice, Sam J. Wilson, Paul D. Bieniasz
Journal: Cell Host & Microbe (2016)

Highlights•ISG screening identifies direct and indirect antiretroviral proteins•Interferon-γ inhibits HIV-1 through IDO1-mediated tryptophan depletion•TRIM56 enhances the antiretroviral potential of interferon-αSummaryInterferons (IFNs) exert their anti-viral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). The activity of known ISGs is insufficient to account for the antiretroviral effects of IFN, suggesting that ISGs with antiretroviral activity are yet to be described. We constructed an arrayed library of ISGs from rhesus macaques and tested the ability of hundreds of individual macaque and human ISGs to inhibit early and late replication steps for 11 members of the retroviridae from various host species. These screens uncovered numerous ISGs with antiretroviral activity at both the early and late stages of virus replication. Detailed analyses of two antiretroviral ISGs indicate that indoleamine 2,3-dioxygenase 1 (IDO1) can inhibit retroviral replication by metabolite depletion while tripartite motif-56 (TRIM56) accentuates ISG induction by IFNα and inhibits the expression of late HIV-1 genes. Overall, these studies reveal numerous host proteins that mediate the antiretroviral activity of IFNs.Graphical abstract
Phase I Trial of Targeted Alpha-Particle Immunotherapy with Actinium-225 (225Ac)-Lintuzumab (Anti-CD33) and Low-Dose Cytarabine (LDAC) in Older Patients with Untreated Acute Myeloid Leukemia (AML)
Authors: Joseph G. Jurcic, Farhad Ravandi, John M. Pagel, Jae H. Park, B. Douglas Smith, Moshe Yair Levy, Elihu H. Estey, Alexander E. Perl, Hagop Kantarjian, Dennis Earle, Dragan Cicic, David A. Scheinberg
Journal: Blood (2015)
Biomodulation of capecitabine by carboplatin and weekly paclitaxel (CCP) in patients with adenocarcinoma of unknown primary (ACUP).
Authors: B. Ahmed, A. Mortazavi, S. Kim, X. Li, R. Liersemann, A. M. Ghany, M. A. Villalona-Calero, T. S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2010)

e13022 Background: ACUP remains a very challenging diagnosis with very little advances over the last two decades. A principal determinant of the therapeutic index with capecitabine-based treatment is the higher expression of thymidine phosphorylase (TP) activity in malignant tissue compared to normal tissue, thus making the active fluoropyrimidine metabolite more tumor specific. Given the observed upregulation of TP by paclitaxel and carboplatin in tumor tissue, the time specificity of this upregulation and the promising results in ACUP from our phase I study of capecitabine in combination with carboplatin and weekly paclitaxel (CCP), we proceeded with a phase II study of CCP in patients with ACUP. Methods: Patients with ACUP received capecitabine 750 mg/m2 bid on days 8-21, paclitaxel 60 mg/m2on days 1, 8, and 15 and carboplatin AUC=6 on day 1 of every 28 days. All patients had a consistent and complete workup to rule out the presence of a primary. We used a minimax 2-stage phase II design of 19 and 17 patients (total 36) with 4 or more responders needed in the first cohort of 19 patients to proceed to the second stage for a total of 36 patients. The primary endpoint for this phase II study was objective response rate per RECIST criteria. Results: 17 patients have enrolled at the Ohio State University so far. Median age for patients was 58 years. There were 7 confirmed responses (1 CR +6 PR) giving an overall response rate of 41% (95% CI: (18%, 65%). Median TTP was 9.3 months (95% CI: [5.5, NA]). There was stabilization of disease in 7 patients with only 3 patients showed evidence of progressive disease as their best response. Most common toxicities were anemia (15 patients), leucopenia/neutropenia (16 patients), thrombocytopenia (14 patients), and nausea (13 patients). Most common grade 3/4 toxicities were leukopenia/neutropenia (6 patients), anemia (4 patients), thrombocytopenia (4 patients), and diarrhea (2 patients).The median number of cycles received was 5.7. Conclusions: Preliminary analysis of our study with CCP in patients with ACUP suggests very interesting activity and acceptable tolerability. We have successfully completed the first stage of the study and are actively accruing to the second stage. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
P2-269: Prediction of response to gemcitabine with polymorphisms of RRM1 gene
Authors: Young-Chul Kim, Soo-Ok Kim, Kyu-Sik Kim, In-Jae Oh, Yu-Il Kim, Sung-Chul Lim, Kyung-Ok Park, Jung-Hwan Lim, Jin-Young Ju, Gye-Jung Cho, Don-Ryeol Chae, Miran Kim, Hyun-Ju Cho
Journal: Journal of Thoracic Oncology (2007)
P3-187: Early Experience of Helical Tomotherapy for Lung Cancer with Multiple Metastatic Lesions
Authors: Ik Jae Lee, Chang Geol Lee, Jae Ho Cho, Ki Chang Keum, Jinsil Seong, Chang Ok Suh, Gwi Eon Kim, Kyungkeun Jeong, Yong Bae Kim
Journal: Journal of Thoracic Oncology (2007)
P-203 KRAS mutational variations and characteristics in colorectal cancer(CRC): Analysis of over 1600 patients in single institute
Authors: E. Shinozaki, Y. Miki, M. Ueno, M. Igarashi, I. Nakayama, H. Osumi, M. Suenaga, K. Chin, M. Ogura, M. Ozaka, S. Matsusaka, D. Takahari, I. Takashi, T. Wakatsuki, T. Yamaguchi, N. Mizunuma
Journal: Annals of Oncology (2015)
Mini-Cog: A brief screening tool for cognitive impairment in older cancer patients.
Authors: M. S. Thein, I. S. Browner, C. Klein, M. Binner, G. R. Shapiro
Journal: Journal of Clinical Oncology (2010)

9064 Background: The incidence of both cancer and cognitive impairment (CI) increases with age. Up to 20% of older cancer patients may have baseline CI, which may be overlooked in a busy oncology practice due to time constraints, staff availability, and complexity of the screening tools. This review compares the prevalence of CI as measured by different screening tools and describes the role of the Mini-Cog (MC) in evaluating CI in older cancer patients. Methods: A retrospective chart review of patients age ≥65 years referred to a Geriatric Oncology clinic with a new diagnosis of solid tumors, lymphoma, or multiple myeloma who had baseline cognitive assessment evaluated by 5 screening tools: Single-item memory question, three-item recall (3IR), clock drawing test (CDT), Mini-Cog (3IR and CDT), and Mini-Mental Status Exam (MMSE). Outcome measures include CI as detected by any of these screening tools and their association with the MMSE score. Results: Participants (n=191) had a mean age of 78 ± 6.6 years (65-99 years) with 68.1% ≥ 75 years, 78% Caucasian, 60.7% women and 51.3% ≥ 12 years of education. Tumor types included breast (33%), colorectal (17%), lung (15%), prostate (9%), and other (26%). 22% had stage IV disease. Among the 77% (n = 147) of patients with a normal MMSE (score >24), 84% had a normal MC, 65% a normal recall and 60% a normal CDT. The overall prevalence of CI in this population was approximately 35%. Conclusions: CI in older cancer patients may be more common than previously expected. Since CI may impact decision making capacity and treatment outcome, identifying CI is essential. The MC is a short and easy to administer screening tool that is not confounded by language or education. Based on our review, the MC may be an effective alternative to the MMSE. Screening for CI with MC should be considered for all older cancer patients. A prospective study to evaluate the applicability of the MC in detecting any CI in this population is warranted. Prevalence of CI by age and screening tools Age (yrs) Memory question Recall CDT MC MMSE 65-74 27.78% 36.07% 38.92% 14.75% 16.39% 75-84 41.18% 40.82% 53.68% 15.18% 24.49% 85-94 34.78% 74.07% 64% 51.85% 29.63% >94 50% 80% 75% 60% 40% Total 36.14% 45.03% 50.82% 28.8% 23.04% No significant financial relationships to disclose.
Optimizing Therapeutic Combinations of a Selective MEK 1/2 Inhibitor (Pimasertib) With PI3K/MTOR Inhibitors or With Multi-Targeted Kinase Inhibitors in Pimasertib-Resistant Human Lung and Colorectal Cancer Cells
Authors: E. Martinelli, T. Troiani, F. Morgillo, E. D'Aiuto, L. Ciuffrida, S. Costantini, L. Vecchione, V. De Vriendt, S. Tejpar, F. Ciardiello
Journal: Annals of Oncology (2012)
Prognostic Factors and Treatment Results After Bleomycin, Etoposide, and Cisplatin in Germ Cell Cancer: A Population-based Study
Authors: Maria G. Kier, Jakob Lauritsen, Mette S. Mortensen, Mikkel Bandak, Klaus K. Andersen, Merete K. Hansen, Mads Agerbaek, Niels V. Holm, Susanne O. Dalton, Christoffer Johansen, Gedske Daugaard
Journal: European Urology (2016)
P0579 : Epidemiological, clinical and virological features of hepatitis delta virus infection in France
Authors: S. Brichler, F. Roudot-Thoraval, D. Samuel, P. Marcellin, O. Chazouilleres, T. Poynard, V. Thibault, F. Zoulim, P. André, N. Ganne, H. Fontaine, Z. Benabdesselam, R. Layese, E. Gordien, D. Roulot
Journal: Journal of Hepatology (2015)
PD-L1 Expression by Two Complementary Diagnostic Assays and mRNA In Situ Hybridization in Small Cell Lung Cancer
Authors: Hui Yu, Cory Batenchuk, Andrzej Badzio, Theresa A. Boyle, Piotr Czapiewski, Daniel C. Chan, Xian Lu, Dexiang Gao, Kim Ellison, Ashley A. Kowalewski, Christopher J. Rivard, Rafal Dziadziuszko, Caicun Zhou, Maen Hussein, Donald Richards, Sharon Wilks, Marc Monte, William Edenfield, Jerome Goldschmidt, Ray Page, Brian Ulrich, David Waterhouse, Sandra Close, Jacek Jassem, Kimary Kulig, Fred R. Hirsch
Journal: Journal of Thoracic Oncology (2016)
Effects of external stress on biodegradable orthopedic materials: A review
Authors: Xuan Li, Chenglin Chu, Paul K. Chu
Journal: Bioactive Materials (2016)

Biodegradable orthopedic materials (BOMs) are used in rehabilitation and reconstruction of fractured tissues. The response of BOMs to the combined action of physiological stress and corrosion is an important issue in vivo since stress-assisted degradation and cracking are common. Although the degradation behavior and kinetics of BOMs have been investigated under static conditions, stress effects can be very serious and even fatal in the dynamic physiological environment. Since stress is unavoidable in biomedical applications of BOMs, recent work has focused on the evaluation and prediction of the properties of BOMs under stress in corrosive media. This article reviews recent progress in this important area focusing on biodegradable metals, polymers, and ceramics.