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Interleukin-2

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https://www.readbyqxmd.com/read/28434398/the-use-of-immunotherapy-in-the-treatment-of-melanoma
#1
REVIEW
Tala Achkar, Ahmad A Tarhini
Patients with advanced melanoma have a compromised anti-tumor immune response leading to tumor immune tolerance and a tumor microenvironment conducive to disease progression. Immunotherapy that successfully overcomes this tumor-mediated immune suppression has made the greatest impact in the management of this disease over the past few years. This progress through immunotherapy builds upon earlier successes that interferon-α had in the treatment of melanoma in the adjuvant setting, as well as that of high-dose interleukin-2 in advanced melanoma...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28428057/natural-killer-cells-differentiated-in-vitro-from-cord-blood-cd34-cells-are-more-advantageous-for-use-as-an-immunotherapy-than-peripheral-blood-and-cord-blood-natural-killer-cells
#2
Anna Domogala, Michael Blundell, Adrian Thrasher, Mark W Lowdell, J Alejandro Madrigal, Aurore Saudemont
BACKGROUND AIMS: Natural killer (NK) cells have the potential to become a successful immunotherapy as they can target malignant cells without being direct effectors of graft-versus-host disease. Our group has previously shown that large numbers of functional NK cells can be differentiated in vitro from umbilical cord blood (CB) CD34(+) cells. To produce a clinically relevant and effective immunotherapy, we hypothesized that it is essential that the NK cells are able to proliferate and persist in vivo while maintaining an optimal activation status and killing capacity...
April 17, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28427014/chemical-and-biological-properties-of-a-supramolecular-complex-of-tuftsin-and-cucurbit-7-uril
#3
Ekaterina A Kovalenko, Ekaterina A Pashkina, Lyubov Y Kanazhevskaya, Alexey N Masliy, Vladimir A Kozlov
Cucurbit[7]uril (CB7) is an uncharged and water-soluble macrocyclic host. CB7 binds to doubly protonated tuftsin, which is the tetrapeptide Thr-Lys-Pro-Arg, with moderate affinity (Ka=2.1×10(3)M(-1)). In this study, the host-guest complexation was confirmed by fluorescence titration. This affinity would allow for easy release of the peptide under physiological conditions. According to density functional theory calculations, the structural binding motif involves hydrogen bonding. The most energetically stable form had the Arg side chain inside the CB7 cavity...
April 17, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28422864/ketamine-as-adjuvant-analgesics-for-patients-with-refractory-cancer-pain-does-affect-il-2-ifn-%C3%AE-expression-of-t-cells-in-vitro-a-prospective-randomized-double-blind-study
#4
Naibao Zhou, Zhijian Fu, Hao Li, Kaiguo Wang
BACKGROUND: Ketamine has been used as an analgesic adjuvant with morphine in the treatment of refractory cancer pain recently. But both morphine and ketamine have been reported to produce a number of immunomodulatory effects. The current study was performed to assess whether the concentration of ketamine, as adjuvant analgesics for patient with refractory cancer pain, was related to its effect on T cells interleukin-2 (IL-2)/interferon-γ (IFN-γ) expression in vitro. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood of patients with refractory cancer pain over a Ficoll-Hypaque density gradient...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28415754/gene-modified-nk-92mi-cells-expressing-a-chimeric-cd16-bb-%C3%AE-or-cd64-bb-%C3%AE-receptor-exhibit-enhanced-cancer-killing-ability-in-combination-with-therapeutic-antibody
#5
Ying Chen, Fengtao You, Licui Jiang, Jialu Li, Xuejun Zhu, Yangyi Bao, Xiang Sun, Xiaowen Tang, Huimin Meng, Gangli An, Bozhen Zhang, Lin Yang
Natural killer (NK) cells play a pivotal role in monoclonal antibody-mediated immunotherapy through the antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. NK-92MI is an interleukin-2 (IL-2)-independent cell line, which was derived from NK-92 cells with superior cytotoxicity toward a wide range of tumor cells in vitro and in vivo. Nonetheless, the Fc-receptor (CD16) that usually mediates ADCC is absent in NK-92 and NK-92MI cells. To apply NK-92MI cell-based immunotherapy to cancer treatment, we designed and generated two chimeric receptors in NK-92MI cells that can bind the Fc portion of human immunoglobulins...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415569/interleukin-2-regulatory-t-cell-axis-critically-regulates-maintenance-of-hematopoietic-stem-cells
#6
Sabrina Giampaolo, Gabriela Wójcik, Edgar Serfling, Amiya K Patra
The role of IL-2 in HSC maintenance is unknown. Here we show that Il2-/- mice develop severe anomalies in HSC maintenance leading to defective hematopoiesis. Whereas, lack of IL-2 signaling was detrimental for lympho- and erythropoiesis, myelopoiesis was enhanced in Il2-/- mice. Investigation of the underlying mechanisms of dysregulated hematopoiesis in Il2-/- mice shows that the IL-2-Treg cell axis is indispensable for HSC maintenance and normal hematopoiesis. Lack of Treg activity resulted in increased IFN-γ production by activated T cells and an expansion of the HSCs in the bone marrow (BM)...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413914/prognostic-value-of-the-soluble-interleukin-2-receptor-level-after-patients-with-follicular-lymphoma-achieve-a-response-to-r-chop
#7
Kento Umino, Shin-Ichiro Fujiwara, Takashi Ikeda, Yumiko Toda, Shoko Ito, Kiyomi Mashima, Daisuke Minakata, Hirofumi Nakano, Ryoko Yamasaki, Yasufumi Kawasaki, Miyuki Sugimoto, Chihiro Yamamoto, Masahiro Ashizawa, Kaoru Hatano, Kazuya Sato, Iekuni Oh, Ken Ohmine, Kazuo Muroi, Yoshinobu Kanda
OBJECTIVES: Follicular lymphoma (FL) is a clinically and biologically heterogeneous disease. Therefore, it is important to identify factors that can predict its clinical outcome. METHODS: We retrospectively evaluated the usefulness of soluble interleukin-2 receptor (sIL-2R) levels after R-CHOP (posttreatment sIL-2R) in 72 patients with newly diagnosed FL who had either a complete response (CR) or partial response. With the use of a recursive partitioning analysis, we determined the cut-off values of post- and pretreatment sIL-2R levels that were associated with disease progression, which corresponded to 486...
April 17, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28413381/delayed-cytoreductive-nephrectomy-following-three-years-of-targeted-therapy-for-metastatic-renal-cell-carcinoma
#8
Ariel Schulman, Mathew Fakhoury, Jean P Wuilleumier, Kevin Becker, Bernadine Donahue, Ruoqing Huang, James Butler, Howard Goodman, Ervin Teper, David Silver
We present a 55-year-old male, with good performance status who was diagnosed with a case of metastatic renal cell carcinoma following a pathologic femur fracture. Despite good performance status, multifocal metastases and poor-prognostic features portended a grim prognosis with predicted overall survival of less than nine months. On initial presentation, he was excluded from cytoreductive nephrectomy based on brain metastasis and interleukin-2 was not pursued as the primary tumor was to be left in situ. The patient was reconsidered for cytoreductive nephrectomy after sustained response to fifth line targeted therapies with shrinkage of tumor burden...
January 2017: Current Urology
https://www.readbyqxmd.com/read/28411126/low-interleukin-2-concentration-favors-generation-of-early-memory-t-cells-over-effector-phenotypes-during-chimeric-antigen-receptor-t-cell-expansion
#9
Tanja Kaartinen, Annu Luostarinen, Pilvi Maliniemi, Joni Keto, Mikko Arvas, Heini Belt, Jonna Koponen, Angelica Loskog, Satu Mustjoki, Kimmo Porkka, Seppo Ylä-Herttuala, Matti Korhonen
BACKGROUND: Adoptive T-cell therapy offers new options for cancer treatment. Clinical results suggest that T-cell persistence, depending on T-cell memory, improves efficacy. The use of interleukin (IL)-2 for in vitro T-cell expansion is not straightforward because it drives effector T-cell differentiation but does not promote the formation of T-cell memory. We have developed a cost-effective expansion protocol for chimeric antigen receptor (CAR) T cells with an early memory phenotype...
April 11, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28406707/moringa-oleifera-rich-diet-and-t-cell-calcium-signaling-in-hypertensive-rats
#10
E S Attakpa, N W Chabi, G A Bertin, J-M Ategbo, B Seri, N A Khan
Moringa oleifera is a plant whose fruits, roots and leaves have been advocated for traditional medicinal uses. The physico-chemical analysis shows that, Moringa contains more dietary polyunsaturated fatty acids (PUFA) than saturated fatty acids (SFA). The consumption of an experimental diet enriched with Moringa oleifera extracts lowered blood pressure in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto (WKY) rats as compared to rats fed an unsupplemented control diet. Anti-CD3-stimulated T-cell proliferation was diminished in both strains of rats fed the Moringa oleifera...
April 12, 2017: Physiological Research
https://www.readbyqxmd.com/read/28406139/t-bet-independent-development-of-ifn%C3%AE-secreting-natural-t-helper-1-cell-population-in-the-absence-of-itk
#11
Arun K Kannan, Sonia Mohinta, Weishan Huang, Lu Huang, Nicholas Koylass, Judith A Appleton, Avery August
Th1, Th2, Th9 and Th17 cells are conventional CD4(+) effector T cells identified as secretors of prototypical cytokines IFNγ, IL4, IL9, and IL-17A respectively. Recently, populations of natural Th17 and Th1 cells (nTh17 and nTh1) with innate-like phenotype have been identified in the thymus that are distinct from conventional Th17 and Th1 cells. The absence of the Tec family kinase Interleukin-2 inducible T cell kinase (Itk) results in T cell immunodeficiency in mice and humans. Here we show that Itk negatively regulates the development of nTh1 cells that express IFNγ in a Tbet independent manner, and whose expansion can be enhanced by IL4...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28395939/a-case-series-of-histoplasmosis-patients-with-elevated-serum-soluble-interleukin-2-receptor-levels
#12
Tatsuro Hirayama, Takahiro Takazono, Kazuma Iwata, Hiroaki Senju, Takaharu Shimazaki, Masato Tashiro, Tomomi Saijo, Takeshi Tanaka, Shigeki Nakamura, Yoshifumi Imamura, Maiko Kojiro, Taiga Miyazaki, Misuzu Tsukamoto, Akitsugu Furumoto, Konosuke Morimoto, Yasunori Muraosa, Yuichi Matsubara, Katsunori Yanagihara, Hiroshi Mukae, Katsuhiko Kamei, Shigeru Kohno, Koichi Izumikawa
Histoplasmosis is a common endemic mycosis that is usually asymptomatic but occasionally results in severe illness. Histoplasmosis and its causative agent, Histoplasma capsulatum, are found worldwide but rarely in Japan. In recent years, however, the number of histoplasmosis patients in Japan has increased. In addition, to our knowledge, there are no previous reports of increased serum soluble interleukin-2 receptor (sIL-2R) levels in patients with histoplasmosis. We report a case series of histoplasmosis in three Japanese temporary workers in Manzanillo, Mexico...
April 8, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28395880/treatment-of-metastatic-uveal-melanoma-with-adoptive-transfer-of-tumour-infiltrating-lymphocytes-a-single-centre-two-stage-single-arm-phase-2-study
#13
Smita S Chandran, Robert P T Somerville, James C Yang, Richard M Sherry, Christopher A Klebanoff, Stephanie L Goff, John R Wunderlich, David N Danforth, Daniel Zlott, Biman C Paria, Arvind C Sabesan, Abhishek K Srivastava, Liqiang Xi, Trinh H Pham, Mark Raffeld, Donald E White, Mary Ann Toomey, Steven A Rosenberg, Udai S Kammula
BACKGROUND: Uveal melanoma is a rare tumour with no established treatments once metastases develop. Although a variety of immune-based therapies have shown efficacy in metastatic cutaneous melanoma, their use in ocular variants has been disappointing. Recently, adoptive T-cell therapy has shown salvage responses in multiple refractory solid tumours. Thus, we sought to determine if adoptive transfer of autologous tumour-infiltrating lymphocytes (TILs) could mediate regression of metastatic uveal melanoma...
April 7, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28393295/elevated-galectin-9-suppresses-th1-effector-function-and-induces-apoptosis-of-activated-cd4-t-cells-in-osteoarthritis
#14
Shufeng Yang, Jin Wang, Fengrong Chen, Guoyin Liu, Zhiqiang Weng, Jianmin Chen
T cell immunoglobulin and mucin domain 3 (Tim-3) is a critical regulatory molecule found on activated Th1 cells, exhausted CD8(+) T cells, and resting monocytes/macrophages. Galectin-9 (Gal-9) is an identified ligand for Tim-3. Interaction between Tim-3 and Gal-9 is thought to inhibit Th1 responses. The regulation and function of Tim-3 and Gal-9 in osteoarthritis (OA) have not been intensively investigated. We found that in peripheral blood, CD4(+) T cells, but not CD8(+) T cells or CD14(+) monocytes, from OA patients presented significantly elevated Tim-3 and Gal-9 expression compared to those from healthy controls (HC)...
April 10, 2017: Inflammation
https://www.readbyqxmd.com/read/28389455/dinutuximab-for-maintenance-therapy-in-pediatric-neuroblastoma
#15
REVIEW
Lauren McGinty, Jill Kolesar
PURPOSE: The pharmacology, clinical efficacy, safety, dosage and administration, and role in therapy of dinutuximab for the treatment of high-risk pediatric neuroblastoma are reviewed. SUMMARY: Dinutuximab (Unituxin, United Therapeutics) is a novel monoclonal antibody recently approved for use in combination with granulocyte- macrophage colony-stimulating factor, interleukin-2, and isotretinoin for the treatment of pediatric patients with high-risk neuroblastoma...
April 15, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28387383/daclizumab-and-its-use-in-multiple-sclerosis-treatment
#16
R Milo, M Osherov
Daclizumab is a humanized monoclonal antibody that binds to the a-subunit (CD25) of the interleukin-2 receptor (IL-2R), thus blocking the formation of the high-affinity IL-2R which is expressed mainly on activated and regulatory T cells. IL-2R modulation by daclizumab results primarily in the expansion of regulatory CD56(bright) natural killer cells that are capable of killing activated T cells, rather than direct suppression of activated T cells. The pharmacokinetic profile of its currently available form, daclizumab high-yield process (DAC-HYP, Zinbryta), suggests high subcutaneous bioavailability, linear pharmacokinetics and an effective half-life suitable for monthly administration...
January 2017: Drugs of Today
https://www.readbyqxmd.com/read/28381754/lymphoplasmacytic-lymphoma-presenting-with-diarrhea-and-joint-pain-which-was-successfully-diagnosed-by-an-myd88-mutation-analysis
#17
Masaya Fukushima, Yasushi Okoshi, Keiko Fukazawa, Mayuko Koshino, Shingo Ishiguro, Shoichi Mitsuhashi, Hitoaki Saitoh, Tatsuo Iijima, Hiroshi Kojima, Mitsuo Hori
A 55-year-old man presented to our department with diarrhea, weight loss, fatigability, and polyarthralgia. Blood tests revealed elevated soluble interleukin-2 receptor levels and IgG-type M protein positivity, without any findings that were suggestive of collagen disease. After computed tomography (CT) detected enlarged lymph nodes in the abdominal para-aortic region, lymphoma was suspected. CT-guided needle biopsy of the lymph node did not help to achieve a definitive diagnosis; however, a bone marrow test showed the pathological features of B-cell lymphoma...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28381173/mesothelin-targeting-chimeric-antigen-receptor-modified-t-cells-by-piggybac-transposon-system-suppress-the-growth-of-bile-duct-carcinoma
#18
Jie-Ying Xu, Zhen-Long Ye, Du-Qing Jiang, Jiang-Chuan He, Yong-Mei Ding, Lin-Fang Li, Sai-Qun Lv, Ying Wang, Hua-Jun Jin, Qi-Jun Qian
Chimeric antigen receptor modified T cell-based immunotherapy is revolutionizing the field of cancer treatment. However, its potential in treating bile duct carcinoma has not been fully explored. Herein, we developed the second-generation mesothelin-targeting chimeric antigen receptor-modified T cells with the 4-1BB co-stimulatory module by the piggyBac transposon system. Mesothelin-targeting chimeric antigen receptor was expressed by 66.0% of mesothelin-targeting chimeric antigen receptor-modified T cells post electrophoretic transfection and stimulation with K562-meso cells; the expressions of activation markers were tested by flow cytometry assay and showed greater activation of mesothelin-targeting chimeric antigen receptor-modified T cells than control T cells (CD107α: 71...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28375782/the-potential-hazardous-effect-of-exposure-to-iron-dust-in-egyptian-smoking-and-non-smoking-welders
#19
Naglaa Abd El Khalik Gobba, Abdel-Maksoud A Hussien, Dalia E El Sharawy, Mohammed Abdalla Hussein
Exposure to iron dust and welding fumes is widespread and may increase the risk of lung inflammation. The aim of this study was to identify associations between exposure to iron/ welding fumes and the levels of inflammatory parameters and allergic mediators among 120 Egyptian males. Forty non-smoking and 40 smoking Egyptian welders as well as 40 healthy volunteers who were never exposed to welding fumes and non-smoking were enrolled in the study. Peak expiratory flow rates (PEFR) that were assessed at the shift of work in the working days revealed an impairment in lung function with the smoking workers showing the worse results, followed by the non-smoking ones as compared to the healthy volunteers...
April 4, 2017: Archives of Environmental & Occupational Health
https://www.readbyqxmd.com/read/28366698/steroid-free-immunosuppression-is-associated-with-enhanced-th1-transcripts-in-kidney-transplantation
#20
Petra Hruba, Irena Tycova, Eva Krepsova, Eva Girmanova, Alena Sekerkova, Janka Slatinska, Ilja Striz, Eva Honsova, Ondrej Viklicky
BACKGROUND: Steroid avoidance in immunosuppression in kidney transplantation offers several metabolic advantages, however it is associated with higher early acute rejection rate. Cellular and molecular mechanisms of this phenomenon remain poorly understood. METHODS: In this single center observational study, low-risk kidney transplant recipients randomized into large multicenter prospective ADVANCE trial with steroid avoidance/early withdrawal and center standard of care treated patients were monitored for 12months...
March 30, 2017: Transplant Immunology
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