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https://www.readbyqxmd.com/read/28343293/pharmacokinetic-and-pharmacodynamic-considerations-in-the-treatment-of-chronic-lymphocytic-leukemia-ibrutinib-idelalisib-and-venetoclax
#1
REVIEW
Madeline Waldron, Allison Winter, Brian T Hill
Management of chronic lymphocytic leukemia has changed markedly over the last several years with the emergence of several novel oral agents targeting B-cell receptor and Bcl-2 signaling pathways. For patients requiring treatment, ibrutinib, idelalisib, and venetoclax offer unique clinical benefits with a different set of therapeutic considerations compared with traditional parenteral therapy. Despite the conveniences afforded by oral therapy, these agents also carry unique logistical obstacles. Drug interactions with agents that are metabolized via the cytochrome P450 3A4 pathway are possible with all three agents...
March 25, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28340071/variable-potassium-concentrations-which-is-right-and-which-is-wrong
#2
Talent Theparee, Robert C Benirschke, Hong-Kee Lee
Reverse pseudohyperkalemia is a term used to describe in vitro, falsely elevated potassium concentrations in plasma specimens that occur in association with extreme leukocytosis and are commonly associated with hematologic malignant neoplasms. Tumor lysis syndrome is an in vivo lysis of tumor cells that leads to elevated levels of potassium, uric acid, phosphate, and lactate dehydrogenase, as well as decreased calcium concentrations. Herein, we report a case of a 66-year-old Caucasian man with stage IV mantle-cell lymphoma who has elevated levels of potassium, uric acid, and phosphorus, as well as a white blood cell (WBC) count greater than 100,000 cells per mm3...
March 6, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/28337749/branched-i%C3%A2-antigens-on-leukemia-cells-enhanced-sensitivity-against-natural-killer-cell-cytotoxicity-through-affecting-the-target-effector-interaction
#3
Yen-Hua Lee, Yi-Jen Liao, Chin-Han Huang, Fu-Ling Chang, Ting-Hsi Fan, Yuh-Ching Twu
BACKGROUND: The aberrant glycosylation on proteins and lipids has been implicated in malignant transformations for promoting the tumorigenesis, metastasis, and evasion from the host immunity. The I-branching β-1,6-N-acetylglucosaminyltransferase, converting the straight i to branched I histo-blood group antigens, reportedly could influence the migration, invasion, and metastasis of solid tumors. STUDY DESIGN AND METHODS: We first chose the highly cytotoxic natural killer (NK)-92MI cells as effector against leukemia for this cell line has been used in several clinical trials...
March 24, 2017: Transfusion
https://www.readbyqxmd.com/read/28335813/tumor-lysis-syndrome-in-an-extraskeletal-osteosarcoma-a-case-report-and-review-of-the-literature
#4
Vito Emanuele Catania, Michele Vecchio, Michele Malaguarnera, Roberto Madeddu, Giulia Malaguarnera, Saverio Latteri
BACKGROUND: This case report describes a spontaneous tumor lysis syndrome due to a rare solid tumor. CASE PRESENTATION: A 65-year-old white woman had tumor lysis syndrome, which represent a dangerous oncological emergency. This syndrome occurs usually with a hematological tumor, but in this case our patient had a solid tumor, which was a rare extraskeletal osteosarcoma, localized in her pelvic region. She also had lung metastases and bilateral hydronephrosis. After spontaneous tumor lysis syndrome, she had acute renal insufficiency, which was treated with hemodialysis and successively with rasburicase, Kayexalate (sodium polystyrene sulfonate), and febuxostat...
March 24, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28323169/isolation-and-characterization-of-human-capg-expressed-and-post-translationally-modified-in-pichia-pastoris
#5
Agnes Papala, Marc Sylvester, Nadine Dyballa-Rukes, Sabine Metzger, Jochen D'Haese
CapG is an actin-binding protein, which is overexpressed in a variety of tumors, i.e. breast, ovarian, pancreatic and lung carcinoma. We successfully expressed human CapG in the wild type strain X-33 of the methylotrophic yeast Pichia pastoris (P. pastoris), which does not express endogenous CapG, in order to characterize this protein in more detail. After mechanical cell lysis, debris was centrifuged and the soluble protein was precipitated with ammonium sulfate. This protein pellet was dialyzed and used for CapG purification...
March 18, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28322863/deep-immune-profiling-by-mass-cytometry-links-human-t-and-nk-cell-differentiation-and-cytotoxic-molecule-expression-patterns
#6
Bertram Bengsch, Takuya Ohtani, Ramin Sedaghat Herati, Niels Bovenschen, Kyong-Mi Chang, E John Wherry
The elimination of infected or tumor cells by direct lysis is a key T and NK cell effector function. T and NK cells can kill target cells by coordinated secretion of cytotoxic granules containing one or both pore-forming proteins, perforin and granulysin and combinations of granzyme (Gzm) family effector proteases (in humans: Gzm A, B, K, M and H). Understanding the pattern of expression of cytotoxic molecules and the relationship to different states of T and NK cells may have direct relevance for immune responses in autoimmunity, infectious disease and cancer...
March 17, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28315060/results-of-a-phase-ib-trial-of-combination-immunotherapy-with-a-cd8-%C3%A2-t-cell-eliciting-vaccine-and-trastuzumab-in-breast-cancer-patients
#7
G Travis Clifton, Jennifer K Litton, Karen Arrington, Sathibalan Ponniah, Nuhad K Ibrahim, Victor Gall, Gheath Alatrash, George E Peoples, Elizabeth A Mittendorf
BACKGROUND: CD8+ T cell-eliciting vaccines are being investigated in breast cancer patients. Preclinical data showed that trastuzumab increases the susceptibility of tumor cells to lysis by vaccine-generated CD8+ T cells, suggesting potential benefit of a combination immunotherapy strategy. The current trial was undertaken to demonstrate the safety of this approach. METHODS: This study was designed as a dose-escalation trial enrolling clinically disease-free, human leukocyte antigen A2+ or A3+ , human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients...
March 17, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28291404/outcomes-and-effectiveness-of-posterior-occipitocervical-fusion-for-suboccipital-spinal-metastases
#8
Panya Luksanapruksa, Jacob M Buchowski, Neill M Wright, Frank H Valone, Colleen Peters, David B Bumpass
OBJECTIVE The incidence of suboccipital spinal metastases is rare but has increased given cancer patients' longer life expectancies. Operative treatment in this region is often challenging because of limited fixation points due to tumor lysis, as well as adjacent neural and vascular anatomy. Few studies have reported on this population of cancer patients. The purpose of this study was to evaluate clinical outcomes and complications of patients with suboccipital spinal metastases who had undergone posterior occipitocervical fixation...
February 24, 2017: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/28291164/severe-case-of-tumor-lysis-syndrome-presenting-spontaneously-in-a-metastatic-pancreatic-adenocarcinoma-patient
#9
Jalaluddin Umar, Aditya Kalakonda, Lauren Panebianco, Gurveen Kaur, Savio John
No abstract text is available yet for this article.
April 2017: Pancreas
https://www.readbyqxmd.com/read/28277671/enzyme-cleavable-polymeric-micelles-for-the-intracellular-de-livery-of-pro-apoptotic-peptides
#10
Hanna B Kern, Selvi Srinivasan, Anthony J Convertine, David Hockenbery, Oliver W Press, Patrick S Stayton
Peptides derived from the third Bcl-2 homology domain (BH3) renormalize apoptotic signaling by antagonizing pro-survival Bcl-2 family members. They serve as a model for potential peptide drugs that possess therapeutic activities but are limited by delivery barriers including short circulation half-lives and poor penetration into cells. A diblock polymeric micelle carrier for the BIM BH3 peptide was recently described that demonstrated anti-tumor activity in a B-cell lymphoma xenograft model [Berguig et al., Mol Ther, 2015]...
March 9, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28274143/avelumab-combining-immune-checkpoint-inhibition-and-antibody-dependent-cytotoxicity
#11
Gerhard Hamilton, Barbara Rath
Immune checkpoint inhibition holds great promise for selected tumors. The human monoclonal antibody (mAB) avelumab is directed to programmed death ligand-1 (PD-L1) and is supposed to inhibit the immunosuppressive PD-L1/PD-1 interaction and, furthermore, effect antibody-dependent cytotoxicity (ADCC) lysis of tumor cells. Areas covered: This article presents an overview of the current means to activate the antitumor immune defense by targeting PD-1 or PD-L1 with mABs and their possible role in ADCC-mediated tumor cell elimination...
April 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28239472/analyses-of-the-peripheral-immunome-following-multiple-administrations-of-avelumab-a-human-igg1-anti-pd-l1-monoclonal-antibody
#12
Renee N Donahue, Lauren M Lepone, Italia Grenga, Caroline Jochems, Massimo Fantini, Ravi A Madan, Christopher R Heery, James L Gulley, Jeffrey Schlom
BACKGROUND: Multiple anti-PD-L1/PD-1 checkpoint monoclonal antibodies (MAb) have shown clear evidence of clinical benefit. All except one have been designed or engineered to omit the possibility to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) as a second potential mode of anti-tumor activity; the reason for this is the concern of lysis of PD-L1 positive immune cells. Avelumab is a fully human IgG1 MAb which has been shown in prior in vitro studies to mediate ADCC versus a range of human tumor cells, and clinical studies have demonstrated anti-tumor activity versus a range of human cancers...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28235628/denosumab-treated-giant-cell-tumor-of-bone-its-histologic-spectrum-and-potential-diagnostic-pitfalls
#13
Pablo Daniel Roitman, Federico Jauk, Germán Luis Farfalli, José Ignacio Albergo, Luis Alberto Aponte-Tinao
Giant cell tumor of bone (GCT) is a locally aggressive, rarely metastasizing primary bone neoplasm that occurs most frequently in the epiphysis of long bones of young adults. It is composed of round, oval or elongated mononuclear cells admixed with osteoclast-like giant cells that express receptor activator of nuclear factor- қB (RANK). The mononuclear stromal cells express RANK ligand (RANKL), a mediator of osteoclast activation. Denosumab, a monoclonal antibody that inhibits RANKL reducing tumor-associated bone lysis, has been used to treat selected cases of GCT...
February 21, 2017: Human Pathology
https://www.readbyqxmd.com/read/28228105/mesenchymal-stromal-cells-as-vehicles-of-tetravalent-bispecific-tandab-cd3-cd19-for-the-treatment-of-b-cell-lymphoma-combined-with-ido-pathway-inhibitor-d-1-methyl-tryptophan
#14
Xiaolong Zhang, Yuanyuan Yang, Leisheng Zhang, Yang Lu, Qing Zhang, Dongmei Fan, Yizhi Zhang, Yanjun Zhang, Zhou Ye, Dongsheng Xiong
BACKGROUND: Although blinatumomab, a bispecific T cell engaging antibody, exhibits high clinical response rates in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (B-ALL) and B cell non-Hodgkin's lymphoma (B-NHL), it still has some limitations because of its short half-life. Mesenchymal stromal cells (MSCs) represent an attractive approach for delivery of therapeutic agents to cancer sites owing to their tropism towards tumors, but their immunosuppression capabilities, especially induced by indoleamine 2,3-dioxygenase (IDO), should also be taken into consideration...
February 23, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28219205/-preparation-of-chaperone-antigen-peptide-vaccine-derived-from-human-gastric-cancer-stem-cells-and-its-immune-function
#15
Y Q Jiang, Q M Guo, X P Xu, J C Liang, Y Y He, S H An, F Su, C Y Li, C X Huang
Objective: To explore the method of extracting chaperone antigen peptide complexes from gastric cancer stem cells and its immune function. Methods: Gastric cancer stem cells and gastric cancer cells were screened by low temperature ultrasonic lysis. After salting out and dialysis, the lysate supernatant was processed with SDS-PAGE to analyze the expression of chaperone antigen peptide complexes, and then was separated and purified with CNBr-activated SepharoseTM 4B. Reverse high pressure liquid chromatography (HPLC), SDS-PAGE and Western blotting were used to analyze the purity and nature of the acquired albumen...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28203093/prevention-and-treatment-of-tumor-lysis-syndrome-and-the-efficacy-and-role-of-rasburicase
#16
REVIEW
Nael Alakel, Jan Moritz Middeke, Johannes Schetelig, Martin Bornhäuser
Tumor lysis syndrome (TLS) is a potentially life-threatening condition that occurs in oncologic and hematologic patients with large tumor burden, either due to cytotoxic therapy or, less commonly, spontaneously because of massive tumor cell lysis. TLS is clinically characterized by acute renal failure, hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. While limited options are available for treating TLS, identifying patients at high risk for developing TLS and prevention in high-risk patients remain an important aspect in the treatment of cancer patients...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28197367/targeting-ewing-sarcoma-with-activated-and-gd2-specific-chimeric-antigen-receptor-engineered-human-nk-cells-induces-upregulation-of-immune-inhibitory-hla-g
#17
Sareetha Kailayangiri, Bianca Altvater, Christian Spurny, Silke Jamitzky, Sonja Schelhaas, Andreas H Jacobs, Constanze Wiek, Katharina Roellecke, Helmut Hanenberg, Wolfgang Hartmann, Heinz Wiendl, Susann Pankratz, Jutta Meltzer, Nicole Farwick, Lea Greune, Maike Fluegge, Claudia Rossig
Activated and in vitro expanded natural killer (NK) cells have substantial cytotoxicity against many tumor cells, but their in vivo efficacy to eliminate solid cancers is limited. Here, we used chimeric antigen receptors (CARs) to enhance the activity of NK cells against Ewing sarcomas (EwS) in a tumor antigen-specific manner. Expression of CARs directed against the ganglioside antigen GD2 in activated NK cells increased their responses to GD2+ allogeneic EwS cells in vitro and overcame resistance of individual cell lines to NK cell lysis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28194289/an-interesting-case-of-intramuscular-myxoma-with-scapular-bone-lysis
#18
Jérôme Tirefort, Frank C Kolo, Alexandre Lädermann
Introduction. Intramuscular myxoma is a rare benign primitive tumor of the mesenchyme founded at the skeletal muscle level; it presents itself like an unpainful, slow-growing mass. Myxomas with bone lysis are even more rare; only 7 cases have been reported in the English literature, but never at the shoulder level. Case Presentation. We describe an 83-year-old patient with a growing mass in the deltoid muscle with unique scapular lysis, without any symptom. Magnetic resonance imaging (MRI) and a biopsy were performed and the diagnosis of intramuscular myxoma has been retained...
2017: Case Reports in Orthopedics
https://www.readbyqxmd.com/read/28194054/tumor-lysis-syndrome-in-multiple-myeloma-an-increasingly-recognized-risk-a-report-of-seven-cases
#19
Abhijai Singh, Shweta Gupta, Barbara Yim, Romy Thekkekara
Tumor lysis syndrome is a constellation of metabolic disturbances commonly seen during therapy of bulky, rapidly proliferative tumors. Multiple myeloma is a low proliferation tumor with rare incidence of tumor lysis syndrome in the pre-Bortezomib era. Post Bortezomib use, a rise in the incidence of tumor lysis has been noted. We present seven cases of tumor lysis syndrome with three patients in spontaneous tumor lysis and four developing the same after chemotherapy. In the previous studies, elevated LDH and deletion of chromosome 13 has been associated with risk of TLS...
March 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28188458/tanapoxvirus-lacking-the-15l-gene-inhibits-melanoma-cell-growth-in-vitro-by-inducing-interferon-%C3%AE-1-release
#20
Tiantian Zhang, Karim Essani
Oncolytic viruses (OVs) have emerged as a promising approach for melanoma treatment by causing tumor lysis and inducing immuno-modulatory activities. Tanapoxvirus (TPV), which causes a mild self-limiting disease in humans and contains a large DNA genome, appears as a promising OV candidate. TPV recombinants were generated with the thymidine kinase/66R gene deletion (TPVΔ66R), the 15L gene deletion (TPVΔ15L), or with both the 15L and 66R gene ablation (TPVΔ15LΔ66R). Our previous studies have shown that treatment of TPVΔ15L resulted in significant tumor regression in xenotransplanted human melanoma in nude mice...
February 10, 2017: Virus Genes
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