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https://www.readbyqxmd.com/read/29137972/circulating-tumoral-dna-preanalytical-validation-and-quality-control-in-a-diagnostic-laboratory
#1
Sergey Nikolaev, Laure Lemmens, Thibaud Koessler, Jean-Louis Blouin, Thierry Nouspikel
We present the results of our technical validation process in establishing the analysis of circulating tumor DNA (ctDNA) as a diagnostic tool. Like most cells in our body, tumor cells shed DNA in the blood flow. Analysis of ctDNA mutational content can provide invaluable information on the genetic makeup of a tumor, and assist oncologists in deciding on therapy, or in following residual disease. However, low absolute amounts of circulating DNA and low tumor fraction constitute formidable analytical challenges...
November 11, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/29132473/-progress-in-clinical-studies-of-chimeric-antigen-receptor-engineered-t-cells-for-treatment-of-childhood-cancer
#2
Ya-Ru Ni, Xiao-Jun Xu, Yong-Min Tang
Nowadays, the 5-year survival rate of childhood cancer patients can be more than 80%, but some patients with relapse and refractory cancers have shown no good response to traditional strategies. Chimeric antigen receptor engineered T (CAR-T) cell therapy is promising for these patients. CAR-T cells recognize the tumor-associated antigens in a non-major histocompatibility complex-restricted manner, so their anti-tumor ability is enhanced. There are four generations of CAR-T cells now. The complete remission rate of pediatric patients with relapse and refractory acute lymphoblastic leukemia can be as high as 90% when treated with CD19-targeting CAR-T cells...
November 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29132013/chimeric-antigen-receptor-modified-t-cells-redirected-to-epha2-for-the-immunotherapy-of-non-small-cell-lung-cancer
#3
Ning Li, Shaohui Liu, Mingjiao Sun, Wei Chen, Xiaogang Xu, Zhu Zeng, Yemin Tang, Yongquan Dong, Alex H Chang, Qiong Zhao
Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) is overexpressed in more than 90% of non-small cell lung cancer (NSCLC) but not significantly in normal lung tissue. It is therefore an important tumor antigen target for chimeric antigen receptors (CAR)-T-based therapy in NSCLC. Here, we developed a specific CAR targeted to EphA2, and the anti-tumor effects of this CAR were investigated. A second generation CAR with co-stimulatory receptor 4-1BB targeted to EphA2 was developed. The functionality of EphA2-specific T cells in vitro was tested with flow cytometry and real-time cell electronic sensing system assays...
November 10, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29130003/spontaneous-tumor-lysis-syndrome-due-to-uterine-leiomyosarcoma-with-lung-metastases
#4
Vivek Alaigh, Debapriya Datta
Tumor lysis syndrome (TLS) is an oncologic emergency characterized by a combination of metabolic derangements (hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia) caused by rapid turnover from cell destruction in certain cancers. These metabolic derangements can lead to seizures, cardiac arrhythmias, renal failure, and death. TLS is usually seen after the initiation of chemotherapy for hematologic malignancies. TLS occurring spontaneously, without initiation of chemotherapy, is rare and its occurrence in solid tumors is rarer still...
2017: Case Reports in Critical Care
https://www.readbyqxmd.com/read/29128997/pd-1-pd-l1-immune-checkpoint-blockade-in-malignant-lymphomas
#5
REVIEW
Yi Wang, Ling Wu, Chen Tian, Yizhuo Zhang
Tumor cells can evade immune surveillance through overexpressing the ligands of checkpoint receptors on tumor cells or adjacent cells, leading T cells to anergy or exhaustion. Growing evidence of the interaction between tumor cells and microenvironment promoted the emergence of immune-checkpoint blockade. By targeting programmed cell death-1 (PD-1) pathway, cytotoxic activity of T cell is enhanced significantly and tumor cell lysis is induced subsequently. Currently, various antibodies against PD-1 and programmed death-ligand 1 (PD-L1) are under clinical studies in lymphomas...
November 11, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29125836/a-simple-in-vitro-tumor-chemosensitivity-assay-based-on-cell-penetrating-peptide-tagged-luciferase
#6
Tingyu Yu, Jiao Lin, Jin Zhao, Wei Huang, Lingwen Zeng, Zhiyuan Fang, Ning Xu
The analysis of intracellular ATP can reveal the response of cells to different treatments and is important for individualized medicine. In the present study, we developed a cell penetrating peptides (CPPs) tagged luciferase (TAT-LUC) for tumor chemosensitivity assay. The activity of recombinant TAT-LUC was evaluated using ATP standard solution and tumor cells. This recombinant TAT-LUC was then used for the analysis of sensitivity index (SI) of four strains of tumor cells. The results showed that TAT-LUC could detect less than 10 nM extracellular ATP with a strong correlation between the luminescence intensity and the ATP content (R2 = 0...
2017: PloS One
https://www.readbyqxmd.com/read/29122155/rituximab-hypersensitivity-evaluation-desensitization-and-potential-mechanisms
#7
Johnson T Wong, Aidan Long
BACKGROUND: Rituximab (Rituxan) hypersensitivity (RITS) can be severe and limits the ability to further administer the treatment. Understanding its pattern and desensitization may permit administration in difficult cases. OBJECTIVE: Analyze RITS patient characteristics, hypersensitivity pattern, and desensitization outcomes to optimize management. METHODS: Twenty-five patients with RITS were referred to the Allergy/Immunology Unit at Massachusetts General Hospital over 5 1/2 years...
November 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/29113227/low-dose-valproic-acid-with-low-dose-gemcitabine-augments-mhc-class-i-related-chain-a-b-expression-without-inducing-the-release-of-soluble-mhc-class-i-related-chain-a-b
#8
Tomoharu Miyashita, Kenji Miki, Takashi Kamigaki, Isamu Makino, Hidehiro Tajima, Shinichi Nakanuma, Hironori Hayashi, Hiroyuki Takamura, Sachio Fushida, Ali K Ahmed, John W Harmon, Tetsuo Ohta
To improve natural killer group 2 member D (NKG2D)-dependent cytotoxicity, the inhibition of cleavage and release of major histocompatibility complex class 1-related chain (MIC) molecules from the tumor surface are required. Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is able to induce cell-surface MICA/B on tumor cells. In the present study, the ability of VPA and gemcitabine (GEM) to upregulate MICA/B in pancreatic cancer cells was investigated, resulting in the inhibition of cleavage and release of MIC molecules from the tumor surface...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29105756/kir-downregulation-by-il-12-15-18-unleashes-human-nk-cells-from-kir-hla-i-inhibition-and-enhances-killing-of-tumor-cells
#9
Eva-Maria Ewen, Jens H W Pahl, Matthias Miller, Carsten Watzl, Adelheid Cerwenka
To exploit autologous NK cells for cancer immunotherapy, it is highly relevant to circumvent killer cell immunoglobulin-like receptor (KIR)-mediated self-inhibition of human NK cells by HLA-I-expressing tumor cells. Here, we show that stimulation of NK cells with IL-12/15/18 for two days leads to downregulation of surface expression of the inhibitory KIR2DL2/L3, KIR2DL1 and KIR3DL1 receptors on peripheral blood NK cells. Downregulation of KIR expression was attributed to decreased KIR mRNA levels which could be re-induced already 3 days after re-culture in IL-2...
November 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29103968/anti-pd-l1-tgf%C3%AE-r2-m7824-fusion-protein-induces-immunogenic-modulation-of-human-urothelial-carcinoma-cell-lines-rendering-them-more-susceptible-to-immune-mediated-recognition-and-lysis
#10
Italia Grenga, Renee N Donahue, Morgan L Gargulak, Lauren M Lepone, Mario Roselli, Marijo Bilusic, Jeffrey Schlom
BACKGROUND: Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma. M7824 is a novel first-in-class bifunctional fusion protein comprising a monoclonal antibody against programmed death-ligand 1 (PD-L1, avelumab), fused to the extracellular domain of human transforming growth factor beta (TGFβ) receptor 2, which functions as a TGFβ "trap." Advanced urothelial tumors have been shown to express TGFβ, which possesses immunosuppressive properties that promote cancer progression and metastasis...
November 2, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29093275/neutralization-of-il-8-decreases-tumor-pmn-mdscs-and-reduces-mesenchymalization-of-claudin-low-triple-negative-breast-cancer
#11
Charli Dominguez, Kristen K McCampbell, Justin M David, Claudia Palena
The complex signaling networks of the tumor microenvironment that facilitate tumor growth and progression toward metastatic disease are becoming a focus of potential therapeutic options. The chemokine IL-8 is overexpressed in multiple cancer types, including triple-negative breast cancer (TNBC), where it promotes the acquisition of mesenchymal features, stemness, resistance to therapies, and the recruitment of immune-suppressive cells to the tumor site. The present study explores the utility of a clinical-stage monoclonal antibody that neutralizes IL-8 (HuMax-IL8) as a potential therapeutic option for TNBC...
November 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/29084163/atomic-resolution-structure-of-the-oncolytic-parvovirus-luiii-by-electron-microscopy-and-3d-image-reconstruction
#12
Nikéa Pittman, Adam Misseldine, Lorena Geilen, Sujata Halder, J Kennon Smith, Justin Kurian, Paul Chipman, Mandy Janssen, Robert Mckenna, Timothy S Baker, Anthony D'Abramo, Susan Cotmore, Peter Tattersall, Mavis Agbandje-McKenna
LuIII, a protoparvovirus pathogenic to rodents, replicates in human mitotic cells, making it applicable for use to kill cancer cells. This virus group includes H-1 parvovirus (H-1PV) and minute virus of mice (MVM). However, LuIII displays enhanced oncolysis compared to H-1PV and MVM, a phenotype mapped to the major capsid viral protein 2 (VP2). This suggests that within LuIII VP2 are determinants for improved tumor lysis. To investigate this, the structure of the LuIII virus-like-particle was determined using single particle cryo-electron microscopy and image reconstruction to 3...
October 30, 2017: Viruses
https://www.readbyqxmd.com/read/29078931/oncologic-metabolic-emergencies
#13
REVIEW
Jonathan Wagner, Sanjay Arora
Cancer and its therapies may lead to several metabolic emergencies that emergency providers (EPs) should be well-versed in identifying and managing. With prompt recognition and treatment initiation in the emergency department, lives can be saved and quality of life maintained. Most oncologic metabolic emergencies occur in advanced cancer states, but some follow initiation of treatment or may be the presenting syndrome that leads to the cancer diagnosis. This article reviews the 2 most emergent oncologic metabolic diagnoses: tumor lysis syndrome and hypercalcemia of malignancy...
December 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/29072078/integrated-multifunctional-electrochemistry-microchip-for-highly-efficient-capture-release-lysis-and-analysis-of-circulating-tumor-cells
#14
Shuangqian Yan, Peng Chen, Xuemei Zeng, Xian Zhang, Yiwei Li, Yun Xia, Jie Wang, Xiaofang Dai, Xiaojun Feng, Wei Du, Bi-Feng Liu
The circulating tumor cells (CTCs) in the blood allow the noninvasive analysis of metastatic mechanisms, cancer diagnosis, prognosis, disease monitoring, and precise therapy through "liquid biopsies". However, there is no integrated and robust multifunctional microchip, which not only could highly efficient capture CTCs, but also fast release and lyse cells on one single chip without using other biochemical agents for downstream biomedical analysis. In this work, we integrated the three functions in one electrochemical microchip (echip) by intentionally designing a cactus-like, topologically structured conductive array consisted of a PDMS micropillar-array core and an electroconductive gold coating layer with hierarchical structure...
November 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29070107/-clinical-analysis-of-7-children-with-mature-b-cell-acute-lymphoblastic-leukemia
#15
Jun Wang, Qin Lu, Lu-Lu He, Xiao-Yan Sun, Meng-Jiao Sun, Yong-Jun Fang
OBJECTIVE: To evaluate the efficacy of CCCG-BNHL-2015 protocol in treatment of children with mature B-cell acute lymphoblastic leukemia (mature B-ALL). METHODS: Seven pediatric patients with newly diagnosed mature B-ALL were treated by CCCG-BNHL-2015 protocol (risk group R4) in Children's Hospital of Nanjing Medical University from November 2014 to January 2017. RESULTS: The median age of patients at initial diagnosis was 7.2 years (range 4...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29067879/expression-of-disialoganglioside-gd2-in-neuroblastic-tumors-a-prognostic-value-for-patients-treated-with-anti-gd2-immunotherapy
#16
Tatjana Terzic, Martine Cordeau, Sabine Herblot, Pierre Teira, Sonia Cournoyer, Mona Beaunoyer, Michel Peuchmaur, Michel Duval, Herve Sartelet
Neuroblastoma, a malignant neoplasm of the sympathetic nervous system, is one of the most aggressive pediatric cancers. Patients with stage IV high-risk neuroblastoma receive an intensive multimodal therapy ending with an immunotherapy based on a chimeric monoclonal antibody ch14.18. Although the use of ch14.18 monoclonal antibody has significantly increased the survival rate of high-risk neuroblastoma patients, about 33% of these patients still relapse and die from their disease. Ch14.18 targets the disialoganglioside, GD2, expressed on neuroblastic tumor (NT) cells...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/29056908/upregulation-of-hla-class-i-expression-on-tumor-cells-by-the-anti-egfr-antibody-nimotuzumab
#17
Greta Garrido, Ailem Rabasa, Cristina Garrido, Lisset Chao, Federico Garrido, Ángel M García-Lora, Belinda Sánchez-Ramírez
Defining how epidermal growth factor receptor (EGFR)-targeting therapies influence the immune response is essential to increase their clinical efficacy. A growing emphasis is being placed on immune regulator genes that govern tumor - T cell interactions. Previous studies showed an increase in HLA class I cell surface expression in tumor cell lines treated with anti-EGFR agents. In particular, earlier studies of the anti-EGFR blocking antibody cetuximab, have suggested that increased tumor expression of HLA class I is associated with positive clinical response...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29053456/localized-electroporation-with-dielectrophoretic-field-flow-fractionation-towards-removal-of-circulating-tumour-cells-from-human-blood
#18
Steven Kinio, James K Mills
This paper presents the design and experimental performance of a microelectrode-based device to selectively lyse cells in a flow in a microfluidic channel. Localized cell lysis is achieved by utilizing "irreversible electroporation", in which cells are exposed to high magnitude electric pulses. Localized cell lysis in a flow has research applications and may allow for removal of harmful cells such as circulating tumor cells from blood. Due to the dependence of this technique on the magnitude of the applied electric field, lethal electric field regions can be localized in the channel by calibration of the applied voltage...
October 17, 2017: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/29050112/-clinical-pathologic-characteristics-and-treatment-outcomes-of-19-relapsed-pediatric-b-cell-lymphoma
#19
S Huang, L Jin, J Yang, Y L Duan, M Zhang, C J Zhou, X L Ma, Y H Zhang
Objective: To review the clinical-pathology characteristics of 19 relapsed pediatric mature B cell lymphoma and to find the risk factors for recurrence and the feasible treatment after relapse. Method: Data of 212 pediatric B cell lymphomas cases in Beijing Children's Hospital from January 2006 to June 2015 were collected retrospectively. All the patients were treated according to the B cell lymphoma regimen of Beijing Children's Hospital. During the study period, 19 of 212 cases were relapsed; the clinio-pathological characteristics of relapsed patients before treatment and after relapse were analyzed retrospectively, the treatment outcomes after relapse were summarized and the patients were followed-up...
October 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29046141/generation-and-characterization-of-a-bispecific-antibody-targeting-both-pd-1-and-c-met
#20
Yi Wu, Min Yu, Zujun Sun, Weihua Hou, Yuxiong Wang, Qingyun Yuan, Wei Mo
Bispecific antibodies, BsAbs, are molecules with the ability to bind to two different epitopes on the same or different antigens. The goal of this study was to create a novel bispecific antibody targeting both cellular-mesenchymal to epithelial transition factor(c-MET) and programmed death-1(PD-1) as an anti-cancer therapeutic candidate. Upon binding to the c-MET antigen on a tumor cell and the PD-1 antigen on a T cell, a BsAb can redirect T cells for tumor killing. Based on the original sequences of PD-1 and c-MET mAbs, a BsAb gene was designed, and cloned into the pCEP4 vector...
October 17, 2017: Protein and Peptide Letters
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