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Effect of interferon-γ-primed mesenchymal stem cells on the growth of acute lymphoblastic leukemia cells in an in vivo model

Cytotherapy 22 May 24

ConclusionWe established four distinct stable cell lines expressing firefly luciferase (fLuci) gene by infection of lentivirus in Jurkat, CCRF-CEM, Sup-T1 and CCRF-HSB2 ALL cells. 105 ALL/fLuci cells together with 106 MSCs were inoculated into NOD/SCID mice by intraperitoneal (IP) injection. And we measured luciferase activity using an IVIS optical imaging technique to determine the effects of MSCs on leukemic mass formation. Much higher luciferase activity was observed when ALL/fLuci cells were co-injected with MSCs as compared to that when ALL/fLuci cells were inoculated alone. In addition, we co-inoculated 105 ALL/fLuci cells with different numbers of MSCs (1:1, 1:5 or 1:10 ratio) into mice. Although the bioluminescent intensity gradually increased in all groups, mice that were co-injected with 106 MSCs showed a higher bioluminescent intensity than those co-injected with lower number of MSCs, indicating the possibility that MSCs play an important role in stimulating a leukemic proliferation. To determine the effects of IFN-γ- priming on the growth of leukemic cells by MSCs, ALL/fLuci cells together with IFN-γ-primed MSCs were inoculated into NOD/SCID mice via intraperitoneal injection. Lower luciferase activity was observed when ALL/fLuci cells were co-injected with IFN-γ-primed MSCs as compared to that when ALL/fLuci cells were co-inoculated with naive MSCs. These results suggest that IFN-γ-priming may activate MSCs’ potential anti-cancer eff...

Conclusion and Future Perspectives This review illustrates our current knowledge of USP7, including its source and characterization, structure, binding partners and substrates in various biological processes. Besides, how USP7 regulates various aspects of a cell under both normal and pathological states are elaborated in detail. As the processes of ubiquitination and deubiquitination are extremely dynamic and context-specific, a series of studies have linked USP7 to different cancers. The biology, particularly the immune oncology mechanisms, reveal that USP7 inhibitors would be useful drugs, thus it is vital to develop hi...

Alla S. Koltsova1,2, Anna A. Pendina1, Olga A. Efimova1*, Olga G. Chiryaeva1, Tatyana V. Kuznetzova1 and Vladislav S. Baranov1,2 1D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia 2Department of Genetics and Biotechnology, Saint Petersburg State University, Saint Petersburg, Russia In the present review, we focus on the phenomenon of chromothripsis, a new type of complex chromosomal rearrangements. We discuss the challenges of chromothripsis detection and its distinction from other chromoanagenesis events. Along with already known causes and mechanisms, we introdu...

Elda Pereira Noronha1†, Luísa Vieira Codeço Marques1†, Francianne Gomes Andrade1, Luiz Claudio Santos Thuler2, Eugênia Terra-Granado1, Maria S. Pombo-de-Oliveira1*† and the Brazilian Collaborative Study Group of Acute Leukemia‡ 1Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil 2Clinical Research Division, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous malignancy, which reflects distinctive stages ...

Conclusions Several model systems are now available to characterize the MSC-tumour interplay in the TME. These offer early promise in establishing robust preclinical platforms for the identification of crucial molecular pathways and for the assessment of clinical efficacy of novel drugs to inhibit cancer development and progression. However, selection of the right model for a given study should be shaped on the purpose, and should also consider fixed biological, biochemical, and biophysical parameters according to the specific tumour type. Finally, in order to get reliable and useful results to be translated to the clinic...

This study included 18 buffy coats collected from volunteer blood donors admitted to the blood transfusion service of IRCCS Bambino Gesù Pediatric Hospital after obtaining informed consent. The Ethical Committee of IRCCS Bambino Gesù Pediatric Hospital approved the study (825/2014) and conducted in accordance with the ethical principles stated in the Declaration of Helsinki. Cells Lines and Cell Culture NK-92 (malignant non-Hodgkin's lymphoma), K562 (chronic myelogenous leukemia, CD19−), Jurkat (acute T cell leukemia, CD19−) Karpas 299 (Human Non-Hodgkin's Ki-positive Large Cell ...

Conclusions The discovery of JAK2V617F mutation in BCR-ABL1-negative MPNs by four different international cooperative groups in 2005 (2–5) led to significant insights on the pathogenesis of these disorders. In fact, this mutation results in a gain-of-function with activation of cytokine and growth factor receptors, and thus of the downstream JAK-STAT pathway (79, 95–98). The JAK2 point mutation in exon 12, present in a small percentage of patients with PV, is able to induce the MPN phenotype through the same pathogenic mechanism (6, 7). In 2006 the MPLW515L/K was reported in ET and PMF patients (44, 45) and d...

Discussion This case demonstrates successful cure of pre-B-ALL complicating XLA by alloSCT with restoration of B-cell development and functional antibody response. We are aware of only one previous case of pre-B-ALL in an XLA patient (21), which suggests that human BTK deficiency in itself does not predispose to pre-B-ALL. However, there are data to suggest that BTK may act as a tumor suppressor, and BTK deficiency may predispose to tumor development following a “second hit.” Mice with a genetic deficiency in Slp65, a gene encoding an adaptor protein that functions together with BTK, have a block in progenito...

Lei Shang1,2 and Minjie Wei1* 1School of Pharmacy, China Medical University, Shenyang, China 2Shenyang Medical College, Shenyang, China The protein lysine methyltransferase SMYD2 has recently emerged as a new enzyme modulate gene transcription or signaling pathways, and involved into tumor progression. However, the role of SMYD2 in drug resistant is still not known. Here, we found that inhibition of SMYD2 by specific inhibitor could enhance the cell sensitivity to cisplatin (CDDP), but not paclitaxel, NVB, and VCR in non-small cell lung cancer (NSCLC). Further study showed that SMYD2 and its substrates were overex...

In this study, based on the whole-genome methylation datasets from The Cancer Genome Atlas (TCGA) and several machine learning methods, we evaluated the possibility of DNA methylation signatures for identifying lymph node metastasis of LUAD, differentiating between tumor tissue and normal tissue, and predicting the overall survival (OS) of LUAD patients. Using the regularized logistic regression, we built a classifier based on the 3616 CpG sites to identify the lymph node metastasis of LUAD. Furthermore, a classifier based on 14 CpG sites was established to differentiate between tumor and normal tissues. Using the Least Ab...

Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...