Wnt/ β‑catenin inhibition reverses multidrug resistance in pediatric acute lymphoblastic leukemia.

Wnt/β‑catenin inhibition reverses multidrug resistance in pediatric acute lymphoblastic leukemia. Oncol Rep. 2018 Dec 04;: Authors: Fu J, Si L, Zhuang Y, Zhang A, Sun N, Li D, Hao B, Ju X Abstract Although ~80% of newly diagnosed pediatric patients with acute lymphoblastic leukemia (ALL) become disease‑free following appropriate treatment, relapses frequently occur, with dismal prognosis. Therefore, it is urgent to develop novel therapeutic modalities. Resistance to chemotherapy is a major obstacle for the treatment of relapsed ALL. It has been indicated that Wnt pathway is potentially associated with leukemia recurrence. In the current study, a vincristine (VCR)‑resistant variant of the human ALL cell line BALL‑1 (BALL‑1/VCR) that also had relatively specific resistance to both doxorubicin and etoposide was generated. Over‑activation of the Wnt/β‑catenin signaling pathway was observed in BALL‑1/VCR cells, whereas Dickkopf‑related protein 1 selectively suppressed the Wnt signaling pathway and sensitized the response of BALL‑1/VCR to anticancer agents. In addition, prednisolone exposure in combination with Wnt inhibition restored chemo‑sensitivity in relapsed ALL blasts. Since the resistance of BALL‑1/VCR cells is potentially attributed to the overexpression of MDR‑associated protein 1 (MRP1), the development of drug resistance in relapsed ALL may associated with the overexpression of MRP1 and P‑glycoprotein. The resul...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

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CONCLUSION: This study showed that the polymorphism of MDR1 C3435T influenced the CSF concentration of MTX in patients with Chinese childhood ALL receiving IV and IT HDMTX treatment.
. PMID: 32053102 [PubMed - as supplied by publisher]
Source: International Journal of Clinical Pharmacology and Therapeutics - Category: Drugs & Pharmacology Tags: Int J Clin Pharmacol Ther Source Type: research
Noncoding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are becoming key parts in the development of multidrug resistance (MDR) in T-cell acute lymphoblastic leukemia (T-ALL). Abnormal ...
Source: Journal of Experimental and Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Research Source Type: research
Conclusion: In the present study, we observed that resveratrol and prednisolone, with a dose-dependent effect, can reduce the expression of the MDR1 protein. This reduction of expression demonstrates that resveratrol and prednisolone can overcome to drug resistance created by MDR1. PMID: 31030491 [PubMed - in process]
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
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...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion In conclusion, F. keratoplasticum and F. petroliphilum were the most frequent species in this study. Amphotericin B showed lower MICs against Fusarium species whereas the antifungal azoles and the fungicide difenoconazole exhibited higher MICs against FSSC. Ethics Statement Samples were collected during routine patient care and the study was retrospective, therefore it was determined by the local Institutional Review Board of the Hospital de Clínicas, Federal University of Paraná and CAPES that ethical clearance was not indicated. Author Contributions PH, AA-H, FQ-T, and JM designed the study....
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Abstract Acute lymphoblastic leukemia (ALL) is the most prevalent cancer among children, and multidrug efflux mediated by overexpression of ABC transporters is the major impediment to successful chemotherapy in this malignancy. The goal of this study is to identify the non-coding RNAs (ncRNAs) which may affect the expression levels of ABCA3; the previously identified prognostic biomarker for multidrug resistance (MDR) in childhood ALL (cALL). Bone marrow samples from 64 cALLs, including 46 de novo and 18 relapsed patients, in addition to 30 non-cancer controls were collected, and ncRNAs were nominated using in sil...
Source: Gene - Category: Genetics & Stem Cells Authors: Tags: Gene Source Type: research
Abstract Galectins are carbohydrate-binding proteins and these have very high affinity for β-galactoside containing glycoproteins and glycolipids. Amongst sixteen types of galectin, the role of galectin 1, 3, 9 and 12 is defined in the development and progression of different types of leukemia including acute myeloid leukemia, acute promyelocytic leukemia, B-cell precursor acute lymphoblastic leukemia, adult T cell leukemia and chronic lymphocytic leukemia. There are multiple mechanisms through which these galectins may affect tumor proliferation. These may include increased production of tumor resistance con...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
We present the P-glycoprotein (P-gp) activity in 2 patients with different outcomes. Both patients had B-cell acute lymphoblastic leukemia; they were responding properly to the treatment, but one of them had an increment in the P-gp activity that correlates with an increment in the disease manifestation, the patient had to be hospitalized and developed sepsis and subsequently died. P-gp levels were correlated with disease progression. P-gp activity needs to be evaluated during treatment to assess and prevent disease relapse or the patient´s death.
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Online Articles: Original Articles Source Type: research
Conclusion: From our preliminary data, the CT genotype of C3435T is associated with a poor ALL outcome while the CC genotype of C1236T is related with an increased incidence of relapse. Although our results provide assistance for oncologist choice of individual therapeutic strategy taking the patient genetic repertoire into consideration, further investigations with larger sample size should be conducted to validate our results. PMID: 30256048 [PubMed - in process]
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
We report the successful treatment of an adolescent male with B-cell lymphoblastic leukemia and MDR invasive sinopulmonary Conidiobolus infection with emphasis on early and aggressive neutrophil support with surgical debridement. The strategies described could be applied to other MDR fungal infections.
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Online Articles: Original Articles Source Type: research
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