scholarly journals Case Report: Long-Term Response to Radiotherapy Combined With Targeted Therapy in Histiocytic Sarcoma Harboring Mutations in MAPK and PI3K/AKT Pathways

2021 ◽  
Vol 11 ◽  
Author(s):  
Zijian Liu ◽  
Yin Xiao ◽  
Xinxiu Liu ◽  
Qiuhui Li ◽  
Tao Liu ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Histiocytic Sarcoma ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
Pathway Enrichment Analysis ◽  
Imatinib Treatment ◽  
Inhibitory Effects ◽  
Poor Overall Survival ◽  
Hematopoietic Malignancy

BackgroundHistiocytic sarcoma (HS) is a rare hematopoietic malignancy with an aggressive clinical presentation associated with a poor overall survival. To date, surgical resection, radiation therapy, and chemotherapy were often utilized for HS, but curative effects are rather disappointing.Case PresentationA 19-year-old female was referred to our hospital with a pathologic diagnosis of HS in December 2017. The patient had a severe airway obstruction resulting from a large mass (6.0 cm × 4.4 cm) arising from the left parapharyngeal space. She did not respond to cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOEP) chemotherapy, then she was switched to radiotherapy and crizotinib according to next-generation sequencing (NGS) results (mutations in MET and MAP2K1). The patient got a partial response after radiotherapy and crizotinib, then she switched to imatinib combined with thalidomide treatment. The patient got a long-term complete response from the treatment and is alive 44 months after initial diagnosis without disease progression. Further KEGG pathway enrichment analysis of NGS results from patient’s tissue revealed that phosphatidylinositol 3′ kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) pathways were activated in this HS patient. We further performed experiments in vitro in a canine histiocytic sarcoma cell line DH82, in order to explore the possible mechanism of imatinib plus thalidomide in HS. Results of cell counting kit-8 (CCK8) assays showed that the proliferation activity of DH82 was significantly inhibited by imatinib but not thalidomide. Combined thalidomide and imatinib treatment did not improve the inhibitory effects of imatinib to DH82. Results of Western blot confirmed the inhibitory effects of imatinib on DH82 by targeting activation of MAPK and PI3K/AKT pathways.ConclusionRadiotherapy combined with targeted therapy guided by NGS may be promising, and further perspective clinical trial is warranted for the localized HS.

Aggressive Treatment in Glioblastoma: What Determines the Survival of Patients?

2020 ◽  
Author(s):  
Lei Yu ◽  
Guozhong Zhang ◽  
Songtao Qi
Keyword(s):  
Overall Survival ◽  
Malignant Gliomas ◽  
Epidemiological Studies ◽  
Control Cohort ◽  
Poor Overall Survival ◽  
Term Survival ◽  
Significant Difference ◽  
Positive Rate ◽  
Long Term Survivors

Abstract Background and Study Aims The exact reason of long-term survival in glioblastoma (GBM) patients has remained uncertain. Molecular parameters in addition to histology to define malignant gliomas are hoped to facilitate clinical, experimental, and epidemiological studies. Material and Methods A population of GBM patients with similar clinical characteristics (especially similar resectability) was reviewed to compare the molecular variables between poor (overall survival [OS] < 18 months, control cohort) and long-term survivors (overall survival > 36 months, OS-36 cohort). Results Long-term GBM survivors were younger. In the OS-36 cohort, the positive rate of isocitrate dehydrogenase (IDH) mutation was very low (7.69%, 3/39) and there was no statistical difference in OS between IDH mutant and wild-type patients. The results of 1p/19q codeletions are similar. Besides, there were no significant difference in MGMT promoter methylation, telomerase reverse transcriptase (TERT) promoter mutation, and TP53 mutations between OS-36 cohort and control cohort. Conclusions No distinct markers consistently have been identified in long-term survivors of GBM patients, and great importance should be attached to further understand the biological characteristics of the invasive glioma cells because of the nature of diffuse tumor permeation.

scholarly journals Bu Shen Zhu Yun Decoction Improves Endometrial Receptivity via VEGFR-2-Mediated Angiogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Li Li ◽  
Huabo Jiang ◽  
Xuecong Wei ◽  
Dandan Geng ◽  
Ming He ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Embryo Implantation ◽  
Mapk Signaling ◽  
Endometrial Receptivity ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
Nuclear Antigen ◽  
Vitro Fertilization

Vascular endothelial growth factor receptor-2 (VEGFR-2) regulates the mitogen-activated protein kinase (MAPK) signaling pathway and plays an important role in angiogenesis. Bu Shen Zhu Yun decoction (BSZYD) can improve endometrial receptivity and embryo implantation rates in patients undergoing in vitro fertilization. However, whether BSZYD improves endometrial receptivity via angiogenesis remains unclear. Here, we investigated the effects of BSZYD on the proliferation, migration, and angiogenesis of human endometrial microvascular endothelial cells (HEMECs) and found that BSZYD upregulated the expression of cyclin D1, matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen (PCNA) in HEMECs. Cell Counting Kit 8 assay, scratch-wound assay, and Tube Formation Assay results showed that BSZYD promoted the proliferation, migration, and angiogenesis of HEMECs. Western blot analysis results revealed the activation of the MAPK signaling pathway by BSZYD through the upregulation of VEGF and VEGFR-2 expression. Together, these findings highlight the novel mechanism underlying BSZYD-mediated improvement in endometrial receptivity through the MAPK signaling pathway.

Long-Term Survival Outcomes of Patients with Small (≤ 1 Centimetre) Node-Negative HER2-Positive Breast Cancer Not Treated with Adjuvant Anti-HER2-Targeted Therapy: A 10-Year Follow-Up Study

Breast Care ◽  
2021 ◽  
Author(s):  
Jenni S. Liikanen ◽  
Marjut Leidenius ◽  
Heikki Joensuu ◽  
Tuomo J. Meretoja
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Disease Free Survival ◽  
Survival Outcomes ◽  
Her2 Expression ◽  
Term Survival ◽  
Node Negative ◽  
Her2 Breast Cancer

Introduction Human epidermal growth factor receptor 2 (HER2) expression is considered an unfavourable prognostic factor in early breast cancer when the patients are not treated with HER2-targeted therapy. However, the long-term prognostic importance of HER2-expression in small (≤1 cm, stage pT1a-b), node-negative HER2+ breast cancer is still incompletely known. Methods A retrospective analysis was performed based on a prospectively collected database including patients with pT1 breast cancer operated at the Helsinki University Hospital, Finland, between March 2000 and April 2006. In this database, 44 patients with pT1a-bN0M0, HER2+ cancer, not treated with adjuvant anti-HER2-targeted therapy (the HER2+ group) and 291 pT1a-bN0M0, hormone receptor positive, HER2- negative cancers (the ER+/HER2- group) were identified and included in the study. Survival outcomes were analysed using the Kaplan-Meier method. Results The median follow-up time was 9.7 years after primary breast surgery. Ten-year distant disease-free survival (DDFS) was 84.0% in the HER2+ group and 98.2% in the ER+/HER2- group (p < 0.001). Ten-year overall survival was only 78.5% in the HER2+ group, but 91.7% in the ER+/HER2- group (p = 0.09). Conclusions Cancer HER2-status is strongly associated with unfavourable DDFS during the first decade of follow-up in patients with small (pT1a-bN0M0) breast cancer when adjuvant anti-HER2-targeted treatment is not administered.

scholarly journals DDX3 Participates in Translational Control of Inflammation Induced by Infections and Injuries

2018 ◽  
Vol 39 (1) ◽  
Author(s):  
Yu-Chang Ku ◽  
Min-Hua Lai ◽  
Chen-Chia Lo ◽  
Yi-Chuan Cheng ◽  
Jian-Tai Qiu ◽  
...  
Keyword(s):  
Translational Control ◽  
Fluorescent Protein ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Reporter ◽  
Antibody Array ◽  
Transgenic Zebrafish ◽  
Pathway Enrichment Analysis ◽  
Translational Efficiency ◽  
Macrophage Migration ◽  
Target Mrnas

ABSTRACT Recent studies have suggested that DDX3 functions in antiviral innate immunity, but the underlying mechanism remains elusive. We previously identified target mRNAs whose translation is controlled by DDX3. Pathway enrichment analysis of these targets indicated that DDX3 is involved in various infections and inflammation. Using immunoblotting, we confirmed that PACT, STAT1, GNB2, Rac1, TAK1, and p38 mitogen-activated protein kinase (MAPK) proteins are downregulated by DDX3 knockdown in human monocytic THP-1 cells and epithelial HeLa cells. Polysome profiling revealed that DDX3 knockdown reduces the translational efficiency of target mRNAs. We further demonstrated DDX3-mediated translational control of target mRNAs by luciferase reporter assays. To examine the effects of DDX3 knockdown on macrophage migration and phagocytosis, we performed in vitro cell migration assay and flow cytometry analysis of the uptake of green fluorescent protein-expressing Escherichia coli in THP-1 cells. The DDX3 knockdown cells exhibited impaired macrophage migration and phagocytosis. Moreover, we used a human cytokine antibody array to identify the cytokines affected by DDX3 knockdown. Several chemokines were decreased considerably in DDX3 knockdown THP-1 cells after lipopolysaccharide or poly(I·C) stimulation. Lastly, we demonstrated that DDX3 is crucial for the recruitment of phagocytes to the site of inflammation in transgenic zebrafish.

scholarly journals Curcumin augments cytostatic and anti-invasive effects of mitoxantrone on carcinosar-coma cells in vitro

2016 ◽  
Vol 63 (3) ◽  
Author(s):  
Marcin Luty ◽  
Edyta Kwiecień ◽  
Magdalena Firlej ◽  
Anna Łabędź-Masłowska ◽  
Milena Paw ◽  
...  
Keyword(s):  
Curcuma Longa ◽  
Drug Resistant ◽  
Additive Effects ◽  
Inhibitory Effects ◽  
Curcumin Treatment ◽  
Invasive Potential ◽  
Effective Doses ◽  
Walker 256

Numerous adverse effects limit the applicability of mitoxantrone for the treatment of drug-resistant tumors, including carcinosarcoma. Here, we estimated the additive effects of mitoxantrone and curcumin, a plant-derived biomolecule isolated from Curcuma longa, on the neoplastic and invasive potential of carcinosarcoma cells in vitro. Curcumin augmented cytostatic, cytotoxic and anti-invasive effects of mitoxantrone on Walker-256 cells. It also strengthened inhibitory effects of mitoxantrone on the motility of drug-resistant Walker-256 cells that had retained the viability after long-term mitoxantrone/curcumin treatment. Thus, curcumin reduces the effective doses of mitoxantrone and augments its interference with the invasive potential of drug-resistant carcinosarcoma cells.

scholarly journals Effects of Long-Term Hydrogen Intervention on Plasma Metabolites and Gut Microbiome of Rats in Health Status

2021 ◽  
Author(s):  
Fei Xie ◽  
Xue Jiang ◽  
Yang Yi ◽  
Zi-Jia Liu ◽  
Chen Ma ◽  
...  
Keyword(s):  
Health Status ◽  
Gut Microbiota ◽  
Biological Effects ◽  
Enrichment Analysis ◽  
The Body ◽  
Plasma Metabolites ◽  
Control Group ◽  
Pathway Enrichment Analysis ◽  
Rrna Gene

Abstract The potential for preventive and therapeutic applications of H2 have now been confirmed in various disease. However, the effects of H2 on health status have not been fully elucidated. Our previous study reported changes in the body weight and 13 serum biochemical parameters during the six-month hydrogen intervention. To obtain a more comprehensive understanding of the effects of long-term hydrogen consumption, the plasma metabolome and gut microbiota were investigated in this study. Compared with the control group, 14 and 10 differential metabolites (DMs) were identified in hydrogen-rich water (HRW) and hydrogen inhalation (HI) group, respectively. Pathway enrichment analysis showed that HRW intake mainly affected starch and sucrose metabolism, and DMs in HI group were mainly enriched in arginine biosynthesis. 16S rRNA gene sequencing showed that HRW intake induced significant changes in the structure of gut microbiota, while no marked bacterial community differences was observed in HI group. HRW intake mainly induced significant increase in the abundance of Lactobacillus, Ruminococcus, Clostridium XI, and decrease in Bacteroides. HI mainly induced decreased abundances of Blautia and Paraprevotella. The results of this study provide basic data for further research on hydrogen medicine. Determination of the effects of hydrogen intervention on microbiota profiles could also shed light on identification of mechanism underlying the biological effects of molecular hydrogen.

scholarly journals Circ-BANP Contributes to Cell Carcinogenesis and Aerobic Glycolysis by Regulating MAPK1 Through miR-874-3p in Colorectal Cancer

2021 ◽  
Author(s):  
Yunxin Zhang ◽  
Kexin Shen ◽  
Hanyi Zha ◽  
Wentao Zhang ◽  
Haishan Zhang
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Xenograft Model ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
Nuclear Antigen ◽  
Luciferase Reporter

Abstract BackgroundCircular RNA-BTG3 associated nuclear protein (circ-BANP) was identifified to involve in cell proliferation of colorectal cancer (CRC). The aerobic glycolysis is a key metabolism mediating cancer progression. However, the role of circ-BANP on aerobic glycolysis in CRC remains unknown. MethodsThe expression of circ-BANP, microRNA (miR)-874-3p, and mitogen-activated protein kinase 1 (MAPK1) mNRA was detected using quantitative real-time polymerase chain reaction. Cell viability and invasion were measured by cell counting kit-8 assay or transwell assay. Glucose consumption and lactate production were assessed by a glucose and lactate assay kit. XF Extracellular Flux Analyzer was used to determine extracellular acidifification rate (ECAR). Western blot was used to analyze the levels of hexokinase-2 (HK2), pyruvate kinase M2 (PKM2), MAPK1, proliferating cell nuclear antigen (PCNA), Cyclin D1, N-cadherin, E-cadherin, hypoxia inducible factor-1α (HIF-1α), glucose transport protein 1(GLUT1), and c-Myc. The interaction between miR-874-3p and circ-BANP or MAPK1 was confifirmed by dual luciferase reporter assay. In vivo experiments were conducted through the murine xenograft model. ResultsCirc-BANP was up-regulated in CRC tissues and cell lines. Circ-BANP knockdown suppressed CRC cell proliferation, invasion and aerobic glycolysis in vitro as well as inhibited tumor growth in vivo. Circ-BANP was a sponge of miR-874-3p and performed anti-tumor effffects by binding to miR-874-3p in CRC cells. Subsequently, we confifirmed MAPK1 was a target of miR-874-3p and circ-BANP indirectly regulated MAPK1 expression by sponging miR-874-3p. After that, we found MAPK1 overexpression partially reversed circ-BANP deletion-mediated inhibition on cell carcinogenesis and aerobic glycolysis in CRC. ConclusionCirc-BANP accelerated cell carcinogenesis and aerobic glycolysis by regulating MAPK1 through miR- 874-3p in CRC, suggesting a promising therapeutic strategy for CRC treatment.

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