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https://www.readbyqxmd.com/read/28350795/fine-mapping-of-the-human-leukocyte-antigen-locus-as-a-risk-factor-for-alzheimer-disease-a-case-control-study
#1
Natasha Z R Steele, Jessie S Carr, Luke W Bonham, Ethan G Geier, Vincent Damotte, Zachary A Miller, Rahul S Desikan, Kevin L Boehme, Shubhabrata Mukherjee, Paul K Crane, John S K Kauwe, Joel H Kramer, Bruce L Miller, Giovanni Coppola, Jill A Hollenbach, Yadong Huang, Jennifer S Yokoyama
BACKGROUND: Alzheimer disease (AD) is a progressive disorder that affects cognitive function. There is increasing support for the role of neuroinflammation and aberrant immune regulation in the pathophysiology of AD. The immunoregulatory human leukocyte antigen (HLA) complex has been linked to susceptibility for a number of neurodegenerative diseases, including AD; however, studies to date have failed to consistently identify a risk HLA haplotype for AD. Contributing to this difficulty are the complex genetic organization of the HLA region, differences in sequencing and allelic imputation methods, and diversity across ethnic populations...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28350690/programmed-death-1-pathway-in-orbital-invasion-of-cutaneous-carcinomas
#2
Edward J Wladis, Joshua A Lee, J Andrew Carlson, Nina Martino, Alejandro P Adam
PURPOSE: The programmed death-1 pathway negatively regulates the immune system. Previous reports have indicated worse tumor-related outcomes with increased expression of the ligand for this pathway. This study was undertaken to assess the role of the PD pathway in cutaneous malignancies that invade the orbit. METHODS: Immunohistochemical staining for the programmed death-1 receptor and ligand was performed on exenteration specimens of invasive cutaneous orbital malignancies (n = 12) and nodular basal cell carcinoma (n = 10)...
March 27, 2017: Ophthalmic Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28346916/pd-1-pd-l1-pathway-in-breast-cancer
#3
Florian Schütz, Stefan Stefanovic, Luisa Mayer, Alexandra von Au, Christoph Domschke, Christof Sohn
No abstract text is available yet for this article.
March 27, 2017: Oncology Research and Treatment
https://www.readbyqxmd.com/read/28346715/cabergoline-related-impulse-control-disorder-in-an-adolescent-with-a-giant-prolactinoma
#4
C Bulwer, R Conn, A Shankar, F Ferrau, S Kapur, A Ederies, M Korbonits, H A Spoudeas
Giant prolactinomas, rare in children, can have devastating endocrine, neurological and visual sequelae. Dopamine agonists (DA) are effective first-line therapy with few side-effects at doses usually used for prolactinoma treatment(1) , but higher-dose therapy for Parkinson's disease has well-recognized associations with impulse control disorders (ICD) including pathological gambling, impulsive eating, compulsive shopping and hypersexuality. Such associations are not well recognized with prolactinomas; to our knowledge this is the first reported case of hypersexuality in an adolescent receiving cabergoline for a giant prolactinoma...
March 27, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28346603/residency-program-directors-interview-methods-and-satisfaction-with-resident-selection-across-multiple-specialties
#5
Tonya VanOrder, Wayne Robbins, Eric Zemper
CONTEXT: Competition for postdoctoral training positions is at an all-time high, and residency program directors continue to have little direction when it comes to structuring an effective interview process. OBJECTIVES: To examine whether a relationship existed between interview methods used and program director satisfaction with resident selection decisions and whether programs that used methods designed to assess candidate personal characteristics were more satisfied with their decisions...
April 1, 2017: Journal of the American Osteopathic Association
https://www.readbyqxmd.com/read/28346602/attitudes-of-family-medicine-program-directors-toward-osteopathic-residents-under-the-single-accreditation-system
#6
Laura K Hempstead, Todd D Shaffer, Karen B Williams, Lt Col James Arnold
BACKGROUND: Between 2015 and 2020, residency programs accredited through the American Osteopathic Association (AOA) are preparing the single graduate medical education (GME) system through the Accreditation Council for Graduate Medical Education (ACGME). OBJECTIVES: (1) To assess the attitudes of family medicine program directors in programs accredited dually by the AOA and ACGME (AOA/ACGME) or ACGME only toward the clinical and academic preparedness of osteopathic residency candidates and (2) to determine program director attitudes toward the perceived value of osteopathic-focused education, including osteopathic manipulative treatment (OMT) curricula...
April 1, 2017: Journal of the American Osteopathic Association
https://www.readbyqxmd.com/read/28346412/vista-is-an-inhibitory-immune-checkpoint-that-is-increased-after-ipilimumab-therapy-in-patients-with-prostate-cancer
#7
Jianjun Gao, John F Ward, Curtis A Pettaway, Lewis Z Shi, Sumit K Subudhi, Luis M Vence, Hao Zhao, Jianfeng Chen, Hong Chen, Eleni Efstathiou, Patricia Troncoso, James P Allison, Christopher J Logothetis, Ignacio I Wistuba, Manuel A Sepulveda, Jingjing Sun, Jennifer Wargo, Jorge Blando, Padmanee Sharma
To date, anti-CTLA-4 (ipilimumab) or anti-PD-1 (nivolumab) monotherapy has not been demonstrated to be of substantial clinical benefit in patients with prostate cancer. To identify additional immune-inhibitory pathways in the prostate-tumor microenvironment, we evaluated untreated and ipilimumab-treated tumors from patients in a presurgical clinical trial. Levels of the PD-L1 and VISTA inhibitory molecules increased on independent subsets of macrophages in treated tumors. Our data suggest that VISTA represents another compensatory inhibitory pathway in prostate tumors after ipilimumab therapy...
March 27, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28346065/effect-of-ultrasonic-treatment-of-palygorskite-on-catalytic-performance-of-pd-cu-palygorskite-catalyst-for-room-temperature-co-oxidation-in-humid-circumstances
#8
Yongzhao Wang, Yongning Wang, Xiao Li, Zhaotie Liu, Yongxiang Zhao
Pd-Cu/palygorskite catalysts were prepared by a wet impregnation method using palygorskite (PC/N-Pal) and ultrasonic treated palygorskite (PC/U-Pal) as the support. Their catalytic activities toward CO oxidation at room temperature and in humid circumstances were investigated. PC/U-Pal exhibits much higher catalytic activity and stability than PC/N-Pal under the conditions of 1.0 vol.% CO and 3.3 vol.% H2O in the feed gas. The XRD results indicate that quartz impurities were eliminated from the palygorskite after the ultrasonic treatment, and more copper species exist in the form of Cu2Cl(OH)3 in PC/U-Pal...
March 27, 2017: Environmental Technology
https://www.readbyqxmd.com/read/28345914/photoreductive-elimination-of-chlorine-from-antimony-in-an-sbpd-vii-complex
#9
Sumit Sahu, Francois P Gabbaï
As part of our ongoing interest in main group species that support the photoreductive elimination of halogens, we have synthesized [Cl3SbVPdIICl2(o-dppp)2] (2, o-dppp = o-(Ph2P)C6H4), a palladium dichloride complex featuring a Lewis acidic trichlorostiborane moiety positioned within the ligand architecture. Upon UV irradiation, this complex undergoes a clean photoreductive chlorine elimination reaction which produces [Cl2SbIVPdICl(o-dppp)2] (1), a complex with a covalent Sb-Pd bond. This transformation illustrates the viability of antimony as an element from which a halogen can be photoeliminated; it also shows that a metal halide can be photolytically coupled with a main group halide to generate a metal-element bond...
March 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28345690/expedient-synthesis-of-a-phenanthro-imidazo-pyridine-fused-heteropolynuclear-framework-via-cdc-coupling-a-new-class-of-luminophores
#10
Biswadip Banerji, Satadru Chatterjee, K Chandrasekhar, Suvankar Bera, Leena Majumder, Chandraday Prodhan, Keya Chaudhuri
We herein report the design and synthesis of a group of fused phenanthro-imidazo[1,2-a]pyridine derivatives as a new class of luminescent materials through a Pd(ii) catalyzed intramolecular CDC (cross dehydrogenative coupling) reaction. This method thus unlocked a convenient & expedient way for the synthesis of a new molecular framework containing π-extended fused heteropolycycles. The heteropolycycles showed very good fluorescence properties both in solid and solution phases which were further utilized in live cell imaging...
March 27, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28345650/rational-combination-of-oncolytic-vaccinia-virus-and-pd-l1-blockade-works-synergistically-to-enhance-therapeutic-efficacy
#11
Zuqiang Liu, Roshni Ravindranathan, Pawel Kalinski, Z Sheng Guo, David L Bartlett
Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector T cells and induces PD-L1 expression on both cancer and immune cells in the tumour...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345313/acute-hyperglycemia-associated-with-anti-cancer-medication
#12
REVIEW
Yul Hwangbo, Eun Kyung Lee
Hyperglycemia during chemotherapy occurs in approximately 10% to 30% of patients. Glucocorticoids and L-asparaginase are well known to cause acute hyperglycemia during chemotherapy. Long-term hyperglycemia is also frequently observed, especially in patients with hematologic malignancies treated with L-asparaginase-based regimens and total body irradiation. Glucocorticoid-induced hyperglycemia often develops because of increased insulin resistance, diminished insulin secretion, and exaggerated hepatic glucose output...
March 2017: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28345023/enhancement-of-psma-directed-car-adoptive-immunotherapy-by-pd-1-pd-l1-blockade
#13
Inna Serganova, Ekaterina Moroz, Ivan Cohen, Maxim Moroz, Mayuresh Mane, Juan Zurita, Larissa Shenker, Vladimir Ponomarev, Ronald Blasberg
Chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies has shown remarkable responses, but the same level of success has not been observed in solid tumors. A new prostate cancer model (Myc-CaP:PSMA(+)) and a second-generation anti-hPSMA human CAR T cells expressing a Click Beetle Red luciferase reporter) were used to study hPSMA targeting and assess CAR T cell trafficking and persistence by bioluminescence imaging (BLI). We investigated the antitumor efficacy of human CAR T cells targeting human prostate-specific membrane antigen (hPSMA), in the presence and absence of the target antigen; first alone and then combined with a monoclonal antibody targeting the human programmed death receptor 1 (anti-hPD1 mAb)...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28344892/clear-cell-ovarian-cancers-with-microsatellite-instability-a-unique-subset-of-ovarian-cancers-with-increased-tumor-infiltrating-lymphocytes-and-pd-1-pd-l1-expression
#14
Brooke E Howitt, Kyle C Strickland, Lynette M Sholl, Scott Rodig, Lauren L Ritterhouse, Dipanjan Chowdhury, Alan D D'Andrea, Ursula A Matulonis, Panagiotis A Konstantinopoulos
Clear cell ovarian carcinoma (CCOC) represents a distinct histologic subtype of ovarian cancer associated with significantly worse prognosis across all stages and no effective therapeutic options. Here, we report a rare but clinically important cohort of CCOCs with microsatellite instability (MSI) (MSI-CCOCs), which are highly immunogenic and may thus be very responsive to immune checkpoint blockade. CCOCs with MSI exhibit a significantly higher number of CD8(+) TILs, higher CD8(+)/CD4(+) ratio, and higher PD-1(+) TILs compared with microsatellite stable (MSS) CCOCs and compared with high grade serous ovarian cancers, which are the most common histologic subtype of ovarian cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344886/car-t-cell-intrinsic-pd-1-checkpoint-blockade-a-two-in-one-approach-for-solid-tumor-immunotherapy
#15
Nan Chen, Aurore Morello, Zachary Tano, Prasad S Adusumilli
PD-L1/2 expression in solid tumors inhibits chimeric antigen receptor (CAR) T-cell efficacy. A PD-1 dominant negative receptor expressed in CAR T cells provides cell-intrinsic checkpoint blockade and augments antitumor efficacy. A combinatorial immunotherapeutic strategy of combining CAR T cells with checkpoint blockade is a promising treatment approach for solid tumors.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344882/tumor-pd-l1-expression-is-correlated-with-increased-tils-and-poor-prognosis-in-penile-squamous-cell-carcinoma
#16
Chuangzhong Deng, Zaishang Li, Shengjie Guo, Peng Chen, Xiaofeng Chen, Qianghua Zhou, Jieping Chen, Xingsu Yu, Xiaoliang Wu, Wenjuan Ma, Qiankun Xie, Yunlin Ye, Yonghong Li, Zike Qin, Zhuowei Liu, Ranyi Liu, Zhenfeng Zhang, Kai Yao, Hui Han, Fangjian Zhou
Despite its rare incidence worldwide, penile squamous cell carcinoma (PeSCC) still presents with significant morbidity and mortality due to the limited treatment options for advanced patients, especially those in developing countries. The program death-1 (PD-1)/PD-1 ligand (PD-L1) axis has been demonstrated to play an important role in tumor immune escape, and immunotherapies targeting this pathway have shown great success in certain cancer types. Here, we analyzed the expression pattern of PD-L1 in tumor cells and tumor-infiltrating lymphocytes (TILs) in PeSCC with a multi-center cohort...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344877/impact-of-chemo-radiotherapy-on-immune-cell-composition-and-function-in-cervical-cancer-patients
#17
H van Meir, R A Nout, M J P Welters, N M Loof, M L de Kam, J J van Ham, S Samuels, G G Kenter, A F Cohen, C J M Melief, J Burggraaf, M I E van Poelgeest, S H van der Burg
New treatments based on combinations of standard therapeutic modalities and immunotherapy are of potential use, but require a profound understanding of immune modulatory properties of standard therapies. Here, the impact of standard (chemo)radiotherapy on the immune system of cervical cancer patients was evaluated. Thirty patients with cervical cancer were treated with external beam radiation therapy (EBRT), using conventional three-dimensional or intensity modulated radiation therapy without constraints for bone marrow sparing...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344873/a-specific-immune-and-lymphatic-profile-characterizes-the-pre-metastatic-state-of-the-sentinel-lymph-node-in-patients-with-early-cervical-cancer
#18
Cédric Balsat, Silvia Blacher, Michael Herfs, Maureen Van de Velde, Nicolas Signolle, Philippe Sauthier, Charles Pottier, Stéphanie Gofflot, Marjolein De Cuypere, Philippe Delvenne, Frédéric Goffin, Agnès Noel, Frédéric Kridelka
The lymph node (LN) pre-metastatic niche is faintly characterized in lymphophilic human neoplasia, although LN metastasis is considered as the strongest prognostic marker of patient survival. Due to its specific dissemination through a complex bilateral pelvic lymphatic system, early cervical cancer is a relevant candidate for investigating the early nodal metastatic process. In the present study, we analyzed in-depth both the lymphatic vasculature and the immune climate of pre-metastatic sentinel LN (SLN), in 48 cases of FIGO stage IB1 cervical neoplasms...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344870/immunological-profiling-of-molecularly-classified-high-risk-endometrial-cancers-identifies-pole-mutant-and-microsatellite-unstable-carcinomas-as-candidates-for-checkpoint-inhibition
#19
Florine A Eggink, Inge C Van Gool, Alexandra Leary, Pamela M Pollock, Emma J Crosbie, Linda Mileshkin, Ekaterina S Jordanova, Julien Adam, Luke Freeman-Mills, David N Church, Carien L Creutzberg, Marco De Bruyn, Hans W Nijman, Tjalling Bosse
High-risk endometrial cancer (EC) is an aggressive disease for which new therapeutic options are needed. Aims of this study were to validate the enhanced immune response in highly mutated ECs and to explore immune profiles in other EC subgroups. We evaluated immune infiltration in 116 high-risk ECs from the TransPORTEC consortium, previously classified into four molecular subtypes: (i) ultramutated POLE exonuclease domain-mutant ECs (POLE-mutant); (ii) hypermutated microsatellite unstable (MSI); (iii) p53-mutant; and (iv) no specific molecular profile (NSMP)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344869/il-15-tim-3-and-nk-cells-subsets-predict-responsiveness-to-anti-ctla-4-treatment-in-melanoma-patients
#20
Rossana Tallerico, Costanza M Cristiani, Elina Staaf, Cinzia Garofalo, Rosa Sottile, Mariaelena Capone, Yago Pico de Coaña, Gabriele Madonna, Eleonora Palella, Maria Wolodarski, Valentina Carannante, Domenico Mallardo, Ester Simeone, Antonio M Grimaldi, Sofia Johansson, Paolo Frumento, Elio Gulletta, Andrea Anichini, Francesco Colucci, Gennaro Ciliberto, Rolf Kiessling, Klas Kärre, Paolo A Ascierto, Ennio Carbone
Despite the success of immune checkpoint blockade in melanoma, the majority of patients do not respond. We hypothesized that the T and NK cell subset frequencies and expression levels of their receptors may predict responses and clinical outcome of anti-CTLA-4 treatment. We thus characterized the NK and T cell phenotype, as well as serum levels of several cytokines in 67 melanoma patients recruited in Italy and Sweden, using samples drawn prior to and during treatment. Survival correlated with low expression of the inhibitory receptor TIM-3 on circulating T and NK cells prior to and during treatment and with the increased frequency of mature circulating NK cells (defined as CD3(-)CD56(dim) CD16(+)) during treatment...
2017: Oncoimmunology
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