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https://www.readbyqxmd.com/read/28344808/safety-tumor-trafficking-and-immunogenicity-of-chimeric-antigen-receptor-car-t-cells-specific-for-tag-72-in-colorectal-cancer
#1
Kristen M Hege, Emily K Bergsland, George A Fisher, John J Nemunaitis, Robert S Warren, James G McArthur, Andy A Lin, Jeffrey Schlom, Carl H June, Stephen A Sherwin
BACKGROUND: T cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s. METHODS: Patients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28344662/nivolumab-in-renal-cell-carcinoma-latest-evidence-and-clinical-potential
#2
REVIEW
Camille Mazza, Bernard Escudier, Laurence Albiges
Similar to melanoma, renal cell carcinoma (RCC) has been historically considered as an immunogenic tumor, with interleukin 2 (IL-2) and interferon alpha (IFN-α) being the first approved treatments in the 1990s. However, these therapies were effective in only 10-20% of cases and were not well tolerated. Recently, new insights on the interaction between the immune system and tumor have identified the programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) pathway to be a key player in evading host immune responses...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28342865/kshv-encoded-viral-interferon-regulatory-factor-4-virf4-interacts-with-irf7-and-inhibits-interferon-alpha-production
#3
Sung-Woo Hwang, DongIk Kim, Jae U Jung, Hye-Ra Lee
Before an infection can be completely established, the host immediately turns on the innate immune system through activating the interferon (IFN)-mediated antiviral pathway. Kaposi's sarcoma-associated herpesvirus (KSHV) utilizes a unique antagonistic mechanism of type I IFN-mediated host antiviral immunity by incorporating four viral interferon regulatory factors (vIRF1-4). Herein, we characterized novel immune evasion strategies of vIRF4 to inhibit the IRF7-mediated IFN-α production. KSHV vIRF4 specifically interacts with IRF7, resulting in inhibition of IRF7 dimerization and ultimately suppresses IRF7-mediated activation of type I IFN...
March 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28340877/adult-t-cell-leukemia-lymphoma-a-problem-abroad-and-at-home
#4
REVIEW
Christopher Dittus, J Mark Sloan
Adult T-cell leukemia/lymphoma (ATLL) is a rare T-cell disorder that is etiologically linked to chronic infection with human T-cell lymphotropic virus type 1. ATLL is divided into four subtypes: acute, lymphomatous, chronic, and smoldering. The acute and lymphomatous variants are often described clinically as the aggressive types of ATLL. Treatment strategies traditionally have focused on antiviral therapy with zidovudine and interferon-alpha and combination chemotherapy. Novel therapeutic approaches include the use of monoclonal antibodies, anti-CCR4 therapy, immunomodulatory therapy, and anti-TAX vaccines...
April 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28336921/different-antiviral-effects-of-ifn%C3%AE-subtypes-in-a-mouse-model-of-hbv-infection
#5
Jingjiao Song, Sheng Li, Yun Zhou, Jia Liu, Sandra Francois, Mengji Lu, Dongliang Yang, Ulf Dittmer, Kathrin Sutter
Interferon alpha (IFNα) is commonly used for the treatment of chronic hepatitis B (CHB) patients. There are 13 different IFNα subtypes in humans, but only the subtype IFNα2 is used for clinical treatment. The antiviral activities of all other IFNα subtypes against HBV have not been studied. To obtain basic knowledge about the direct antiviral as well as the immunomodulatory effects of IFNα subtypes, we used the HBV hydrodynamic injection (HI) mouse model. Application of most IFNα subtype proteins inhibited HBV replication in vivo, with IFNα4 and IFNα5 being the most effective subtypes...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28321817/adverse-events-in-cancer-immunotherapy
#6
Noha Abdel-Wahab, Anas Alshawa, Maria E Suarez-Almazor
Cancer immunotherapy has resulted in durable responses in patients with metastatic disease, unseen with traditional chemotherapy. Several therapies have been approved by the Food and Drug Administration for the treatment of various cancers, including: immune checkpoint inhibitors, cytokines - interleukin 2 (IL-2) and interferon alpha (IFN), and the cancer vaccine sipuleucel-T. These therapies upregulate the immune system to enhance antitumor responses. As a consequence, they can cause inflammatory and immune-related adverse events that can affect one or more organs, can be serious, and on occasion lifethreatening...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28314304/narcoleptic-like-episodes-in-a-patient-receiving-pegylated-interferon-alpha-2b-a-case-report-and-review-of-literature
#7
Benjamin O Lawson, Hung T Khong
A 26-year-old male developed narcoleptic-like episodes while on pegylated interferon-alpha 2b (peg-IFN-α2b) therapy for stage IIIB melanoma. Once peg-IFN-α2b was discontinued, the narcoleptic-like episodes eradicated. A case report and review of the literature are presented in this article.
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28295835/type-i-interferons-modulate-methotrexate-resistance-in-gestational-trophoblastic-neoplasia
#8
Kevin M Elias, Richard A Harvey, Kathleen T Hasselblatt, Michael J Seckl, Ross S Berkowitz
PROBLEM: Resistance to methotrexate is a leading clinical problem in gestational trophoblastic neoplasia (GTN), but there are limited laboratory models for this condition. METHOD OF STUDY: We created isogenic trophoblastic cell lines resistant to methotrexate and compared these to the parent cell lines using gene expression microarrays and qRT-PCR followed by mechanistic studies using recombinant cytokines, pathway inhibitors, and patient sera. RESULTS: Gene expression microarrays and focused analysis by qRT-PCR revealed methotrexate led to type I interferon upregulation, in particular interferon alpha 2 (IFNA2), and methotrexate resistance was associated with chronic low level increases in type I interferon expression...
March 14, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28292947/mobilization-of-allogeneic-peripheral-blood-stem-cell-donors-with-intravenous-plerixafor-mobilizes-a-unique-graft
#9
Mark A Schroeder, Michael P Rettig, Sandra Lopez, Stephanie Christ, Mark Fiala, William Eades, Fazia A Mir, Jin Shao, Kyle McFarland, Kathryn Trinkaus, William Shannon, Elena Deych, Jinsheng Yu, Ravi Vij, Keith Stockerl-Goldstein, Amanda F Cashen, Geoffery L Uy, Camille N Abboud, Peter Westervelt, John F DiPersio
A single subcutaneous (SC) injection of plerixafor results in rapid mobilization of hematopoietic progenitors but fails to mobilize 33% of normal allogeneic sibling donors in one apheresis. We hypothesized that changing the route of administration of plerixafor from SC to intravenous (IV) may overcome the low stem cell yields and allow collection in one day. A phase I trial followed by a phase II efficacy trial was conducted in allogeneic sibling donors. The optimal dose of IV plerixafor was determined to be 0...
March 14, 2017: Blood
https://www.readbyqxmd.com/read/28292546/novel-insights-into-host-responses-and-reproductive-pathophysiology-of-porcine-reproductive-and-respiratory-syndrome-caused-by-prrsv-2
#10
REVIEW
John C S Harding, Andrea Ladinig, Predrag Novakovic, Susan E Detmer, Jamie M Wilkinson, Tianfu Yang, Joan K Lunney, Graham S Plastow
A large challenge experiment using North American porcine reproductive and respiratory virus (PRRSV-2) provided new insights into the pathophysiology of reproductive PRRS. Deep phenotyping of dams and fetuses identified maternal and fetal predictors of PRRS severity and resilience. PRRSV infection resulted in dramatic decreases in all leukocyte subsets by 2days post inoculation. Apoptosis in the interface region was positively related to endometrial vasculitis, viral load in endometrium and fetal thymus, and odds of meconium staining...
March 2, 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28292536/topical-interferon-alpha-2b-topic-as-the-first-therapeutic-option-in-a-clinical-case-of-conjunctival-intraepithelial-neoplasia
#11
S Pagán Carrasco, D Arranz Maestro
INTRODUCTION: Conjunctival intraepithelial neoplasia is a pre-malignant lesion of the ocular surface. It can be treated with topical interferon alpha-2b (INF α-2b) as first choice. CLINICAL CASE: A 71-year-old man referred for corneal-conjunctival, gelatinous lesion in the left eye (LE) with an area of almost 270°. The clinical diagnosis was compatible with a corneal-conjunctival intraepithelial neoplasia. Topical treatment was started with INF α-2b at a dose of one million international units (IU)/ml, 4 times/day for 4 months, with remission being achieved...
March 11, 2017: Archivos de la Sociedad Española de Oftalmología
https://www.readbyqxmd.com/read/28289093/a-hot-spot-on-interferon-alpha-beta-receptor-subunit-1-ifnar1-underpins-its-interaction-with-interferon-%C3%AE-and-dictates-signaling
#12
Nicole A de Weerd, Antony Y Matthews, Phillip R Pattie, Nollaig M Bourke, San S Lim, Julian P Vivian, Jamie Rossjohn, Paul J Hertzog
The interaction of IFN-β with its receptor IFNAR1 is vital for host-protective anti-viral and anti-proliferative responses, but signaling via this interaction can be detrimental if dysregulated. While it is established that IFNAR1 is an essential component of the IFNAR signaling complex, the key residues underpinning the IFN-β-IFNAR1 interaction are unknown. Guided by the crystal structure of the IFN-β-IFNAR1 complex, we used truncation variants and site directed mutagenesis to investigate domains and residues enabling complexation of IFN-β to IFNAR1...
March 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28285495/pharmacological-interventions-for-acute-hepatitis-c-infection-an-attempted-network-meta-analysis
#13
REVIEW
Maria Kalafateli, Elena Buzzetti, Douglas Thorburn, Brian R Davidson, Emmanuel Tsochatzis, Kurinchi Selvan Gurusamy
BACKGROUND: Hepatitis C virus (HCV) is a single-stranded RNA (ribonucleic acid) virus that has the potential to cause inflammation of the liver. The traditional definition of acute HCV infection is the first six months following infection with the virus. Another commonly used definition of acute HCV infection is the absence of HCV antibody and subsequent seroconversion (presence of HCV antibody in a person who was previously negative for HCV antibody). Approximately 40% to 95% of people with acute HCV infection develop chronic HCV infection, that is, have persistent HCV RNA in their blood...
March 13, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28282804/ifnar1-expression-level-in-iranian-multiple-sclerosis-patients-treated-with-ifn-b
#14
Arezou Sayad, Mohsen Khakzad Kelarijani, Elham Sajjadi, Mohammad Taheri
BACKGROUND: Multiple sclerosis (MS) as an auto-immune disease is an inflammatory, demyelinating disease of the central nervous system. Certain genes have shown to be involved in the initiation of MS but the specific role of some of them, e.g. IFNAR1 has not been identified in certain populations yet. OBJECTIVE: The IFNAR1 as a type I membrane protein shapes one of the two chains of a receptor for interferons alpha and beta. METHODS: To find out how IFNAR1 functions in the Iranian population, the researchers compared the expression level of this gene in relapsing-remitting MS (RR-MS) samples with normal individuals...
March 3, 2017: Human Antibodies
https://www.readbyqxmd.com/read/28275599/ocular-surface-squamous-neoplasia-associated-with-atopic-keratoconjunctivitis
#15
Ankit Shah, Edgar M Espana, Arun D Singh
PURPOSE: To describe 2 cases of invasive squamous cell carcinoma that originated in the setting of severe atopic keratoconjunctivitis (AKC). METHODS: Case one involved a 73-year-old male with atopic eczema and severe AKC who developed a limbal lesion suspicious for ocular surface squamous neoplasia (OSSN). Slit-lamp examination was significant for a new sessile lesion in the temporal limbal region of the left eye. The lesion was treated with excisional biopsy and cryotherapy...
January 2017: Ocular Oncology and Pathology
https://www.readbyqxmd.com/read/28270340/adult-t-cell-leukemia-lymphoma-treatment-in-bahia-brazil
#16
Pedro Dantas Oliveira, Ítala Gomes, Victor Hugo Gomes Souza, Ernesto Cunha Pires, Glória Bomfim Arruda, Achiléa Bittencourt
BACKGROUND: Adult T-cell leukemia/lymphoma is a peripheral disease associated with human T-cell lymphotropic virus type 1. Treatment is carried out according to clinical type with watchful waiting being recommended for less aggressive types. Aggressive adult T-cell leukemia/lymphoma is generally treated with chemotherapy and/or antivirals. The objective of this study was to correlate the survival of patients diagnosed in Bahia, Brazil, with the therapeutic approaches employed and to evaluate what issues existed in their treatment processes...
January 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/28268259/intravesical-bacillus-calmette-gu%C3%A3-rin-with-interferon-alpha-versus-intravesical-bacillus-calmette-gu%C3%A3-rin-for-treating-non-muscle-invasive-bladder-cancer
#17
REVIEW
Andrew Rh Shepherd, Emily Shepherd, Nicholas R Brook
BACKGROUND: Despite local therapies, commonly transurethral resection (TUR) followed by adjuvant treatments, non-muscle-invasive bladder cancer (NMIBC) has a high rate of recurrence and progression. Intravesical Bacillus Calmette-Guérin (BCG) has been shown to reduce recurrence and progression in people with NMIBC following TUR, however many people do not respond to treatment, have recurrence shortly after, or cannot tolerate standard-dose therapy. The potential for synergistic antitumour activity of interferon (IFN)-alpha (α) and BCG provides some rationale for combination therapy for people who do not tolerate or respond to standard-dose BCG therapy...
March 8, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28256466/evaluation-of-the-effects-of-omega-3-interferon-alpha-2b-administration-on-partial-bladder-outlet-obstruction-in-a-rat-model
#18
Fatih Firat, Nihat Uluocak, Fikret Erdemir, Dogan Atilgan, Fatma Markoc, Bekir Suha Parlaktas, Adem Yasar
BACKGROUND & OBJECTIVES: In bladder outlet obstruction-induced rat models, the transforming growth factor-beta (TGF-β) and collagen ratios have been shown to be increased. Increased TGF-β leads to fibrosis. In this study, the effect of omega-3 and interferon alpha-2b (IFN α-2b) was investigated on oxidative stress, inflammation and fibrosis in bladder structure in a partial bladder outlet obstruction (PBOO) rat model. METHODS: A total of 35 male Wistar albino rats, weighing 300-350 g, were used in the study...
October 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28254519/assessment-of-the-structure-of-pegylated-recombinant-protein-therapeutics-by-the-nmr-fingerprint-assay
#19
Derek J Hodgson, Yves Aubin
A number of recombinant protein therapeutic products, such as filgrastim (methionyl granulocyte colony stimulating factor [Met-GCSF] used to boost the immune system in chemotherapy treated cancer patients), and interferon alpha-2 (used for the treatment of various viral infections), have been chemically modified with the addition of a polyethylene glycol (PEG) chain. This modification prolongs residency of the drug in the body and reduces metabolic degradation, which allows less frequent administration of the products...
February 16, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28253324/interferon-alpha-treatment-stimulates-interferon-gamma-expression-in-type-i-nkt-cells-and-enhances-their-antiviral-effect-against-hepatitis-c-virus
#20
Eisuke Miyaki, Nobuhiko Hiraga, Michio Imamura, Takuro Uchida, Hiromi Kan, Masataka Tsuge, Hiromi Abe-Chayama, C Nelson Hayes, Grace Naswa Makokha, Masahiro Serikawa, Hiroshi Aikata, Hidenori Ochi, Yuji Ishida, Chise Tateno, Hideki Ohdan, Kazuaki Chayama
Interferon (IFN) inhibits hepatitis C virus (HCV) replication through up-regulation of intrahepatic IFN-stimulated gene expression but also through activation of host immune cells. In the present study, we analyzed the immune cell-mediated antiviral effects of IFN-α using HCV-infected mice. Urokinase-type plasminogen activator (uPA)-severe combined immunodeficiency (SCID) mice with transplanted human hepatocytes were infected with genotype 1b HCV and injected with human peripheral blood mononuclear cells (PBMCs)...
2017: PloS One
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