Expression profile, clinical significance and biological functions of IGF2BP2 in esophageal squamous cell carcinoma

xlomafota13 shared this article with you from Inoreader Expression profile, clinical significance and biological functions of IGF2BP2 in esophageal squamous cell carcinoma Via Experimental and therapeutic medicine Exp Ther Med. 2022 Apr;23(4):252. doi: 10.3892/etm.2022.11177. Epub 2022 Feb 1. ABSTRACT The ectopic expression of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has been demonstrated to facilitate tumorigenesis and induce proliferation in a various types of cancer. However, the role of IGF2BP2 in esophageal squamous cell carcinoma (ESCC) has yet been fully elucidated. In this regard, the current study assessed the expression patterns and clinical significance of IGF2BP2 in 94 Chinese patients diagnosed with ESCC. Immunohistochemistry and reverse transcription-quantitative PCR assays were employed to assess IGF2BP2 expression in ESCC tissues compared with adjacent healthy tissues. The results revealed that the protein expression of IGF2BP2 was substantially upregulated in ESCC tissues compared with adjacent ESCC tissues. More specifically, higher IGF2BP2 expression strongly associated with tumor node metastasis stage, ly mphatic infiltration and lymph node metastasis. Using two ESCC cell lines (TE-1 and TE-10), the inhibition of IGF2BP2 expression by small interfering RNA was proven to induce apoptosis and suppress proliferation, migration and cell cycle progression in vitro. Collectively, the present findings indicated that IGF2BP2 may serve a major role in the development of ESCC carcinogenesis. The present study may be helpful in the design of potential drug targets in the treatment of ESCC. PMID:35261624 | PMC:PMC8855499 | DOI:10.3892/etm.2022.11177 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cofilin-1 as a potential biomarker for Mycobacterium tuberculosis infection

xlomafota13 shared this article with you from Inoreader Cofilin-1 as a potential biomarker for <em>Mycobacterium tuberculosis</em> infection Via Experimental and therapeutic medicine Exp Ther Med. 2022 Apr;23(4):253. doi: 10.3892/etm.2022.11178. Epub 2022 Feb 1. ABSTRACT Tuberculosis (TB) induced by Mycobacterium tuberculosis (M. tb), is one of the deadliest human infections worldwide. Our previous studies demonstrated cofilin-1 (CFL1) expression was significantly increased in exosomes from Mycobacterium avium (M. avium)-infected macrophages. The expression of CFL1 protein in M. tb infected hosts was investigated in the present study to predict whether CFL1 could have potential as a biomarker for M. tb infection. In the present study, the mRNA and protein expression levels of CFL1 in M. avium-infected macrophages and supernatants were analyzed via reverse transcription-quantitative PCR and western blotting. Furthermore, CFL1 expression in macrophages was knocked down in vivo, and then CFL1 expression levels in M. avium-infected macrophages and supernata nt were detected via western blotting and ELISA. In addition, CFL1 was detected in the peripheral blood mononuclear cells and plasma of patients with TB using western blotting and ELISA. The specificity and sensitivity of CFL1 as a biomarker and the association between TB infection and normal individuals were compared and analyzed using GraphPad Prism 5. CFL1 protein expression levels were significantly increased in M. avium-infected macrophages and supernatant. Meanwhile, CFL1 was upregulated in patients with TB. Bioinformatics statistics indicated the high specificity and sensitivity of CFL1 in patients with TB. Thus, these results suggest that CFL1 may act as a potential biomarker of TB infection. PMID:35261625 | PMC :PMC8855514 | DOI:10.3892/etm.2022.11178 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Recombinant cell-detecting RaDR-GFP in mice reveals an association between genomic instability and radiation-induced-thymic lymphoma

xlomafota13 shared this article with you from Inoreader Recombinant cell-detecting RaDR-GFP in mice reveals an association between genomic instability and radiation-induced-thymic lymphoma Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):562-573. eCollection 2022. ABSTRACT In this study, we aimed to investigate how homologous recombinant (HR)-related genomic instability is involved in ionizing radiation (IR)-induced thymic lymphoma in mice. We divided five-week-old Rosa26 Direct Repeat-GFP (RaDR-GFP) transgenic mice into non-IR control and IR groups and exposed the mice in the IR group to a 7.2 Gy dose of γ-rays, delivered in 1.8 Gy fractions, once a week for four weeks. We then estimated mouse survival and recorded their body, thymus, and spleen weights. The frequency of HR events in the chromosomes of the thymus, bone marrow, and spleen cells and the phenotype of thymic lymphoma cells were analyzed using fluorescence-activated cell sorting (FACS). We found that most mice in the IR group developed thymic lymphoma, their survival rate decreasing to 20% after 180 days of IR exposure, whereas no mice died in the non-IR control group un til day 400. The thymus and spleen weighed significantly more in the IR-4-month group than that in the non-IR group; however, we observed no significant differences between the body weights of the control and IR mice. FACS analysis indicated that the frequency of HR events significantly increased at two and four months after the last IR dose in the bone marrow and thymus cells, but not in the spleen cells of RaDR-GFP transgenic mice, suggesting that recombinant cells accumulated in the thymus upon IR exposure. This suggests that IR induces genome instability, revealed as increased HR, that drives the development of thymic lymphoma. Additionally, phenotypic analysis of lymphoma cells showed an increase in the CD4-/CD8+ (CD8SP) cell population and a decrease in the CD4+/CD8- (CD4SP) cell population in the IR-4-month group compared to that in the non-IR group, indicating that IR induces an aberrant cell phenotype characteristic of lymphoma. I n conclusion, we observed a significant increase in HR events and abnormal phenotype in thymic lymphoma cells at two and four months after IR exposure in both the thymus and bone marrow tissues, suggesting that genomic instability is involved in the early stages of thymic lymphomagenesis. Our study indicates that HR-visualizing RaDR-GFP transgenic mice can help explore the links between the molecular mechanisms of genome instability and IR-induced tumorigenesis. PMID:35261787 | PMC:PMC8899999 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Multimodality imaging in the assessment of bone marrow-derived mesenchymal stem cell therapy for doxorubicin-induced cardiomyopathy

xlomafota13 shared this article with you from Inoreader Multimodality imaging in the assessment of bone marrow-derived mesenchymal stem cell therapy for doxorubicin-induced cardiomyopathy Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):574-584. eCollection 2022. ABSTRACT Due to their broad-spectrum effects and high antitumor efficacies, anthracycline-based chemotherapies are commonly prescribed in various solid and hematological malignancies. Doxorubicin (DOX) is one of the most highly used anthracyclines but has been shown to cause lethal cardiomyopathy in clinical practice. Studies have demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to rescue DOX-induced cardiomyopathy (DIC). However, novel molecular imaging techniques are required to explore the biological behaviors, safety, eventual viability, and environmental interactions of transplanted stem cells during therapy. To investigate the biological behaviors of transplanted BMSCs, we applied bioluminescence imaging (BLI) and magnetic resonance imaging (MRI) techniques to trace firefly luciferase (Fluc) and ultrasmall superparamagnetic iron oxi de (USPIO) double-labeled mouse BMSCs after injection into the heart apex in a chronic DIC mouse model. Then, we determined the optimal BMSC number for transplantation into the heart and optimized MRI parameters to evaluate transplanted BMSCs in vitro and in vivo. Our results showed that the BLI trace signal could last 7 days in the DIC mouse model, whereas the MRI signal lasted up to 3 days. However, MRI provided more detailed pathophysiological information on DIC than BLI, such as inflammation and fibrosis signs. The optimal in vivo cell number for BLI and MRI was determined to be 1×106. In conclusion, BLI combined with multimodality MRI could be used to monitor the biological behavior of BMSCs transplanted into a chronic DIC mouse model in a visual and dynamic manner. PMID:35261788 | PMC:PMC8899982 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A novel HDAC11 inhibitor potentiates the tumoricidal effects of cordycepin against malignant peripheral nerve sheath tumor through the Hippo signaling pathway

xlomafota13 shared this article with you from Inoreader A novel HDAC11 inhibitor potentiates the tumoricidal effects of cordycepin against malignant peripheral nerve sheath tumor through the Hippo signaling pathway Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):873-892. eCollection 2022. ABSTRACT Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder. Clinically, the hallmarks of NF1 include skin pigmentation and cutaneous neurofibroma. Some NF1 patients develop plexiform neurofibroma (PN) since early childhood. Pathologically, PN contains abundant Schwann cells, blood vessels and connective tissues, which may transform into a malignant peripheral nerve sheath tumor (MPNST). MPNST is a highly invasive sarcoma without any effective therapy. Recently, both in vitro and in vivo studies showed that cordycepin can inhibit the growth of MPNST cells. Cordycepin causes cell cycle arrest at G2/M phase and downregulates the protein levels of α-tubulin, p53 and Sp1. Herein, the present study revealed that the HDAC11 inhibitor, FT895, can synergistically enhance the tumoricidal effect of cordycepin against MPNST cells in vitro< /i>. Treatment with the combination of cordycepin and FT895 reduced the size of MPNST in the xenograft mouse model. The combined treatment decreased the protein levels of α-tubulin and KIF18A, which may disrupt the microtubule organization leading to the mis-segregation of chromosomes and aneuploidy. Moreover, the expression levels of TEAD1 and its co-activator TAZ, the candidate proteins in hippo signaling pathway, were suppressed after combined treatment. Sequence analysis found a few binding sites for the transcription factor, TEAD1 in the promoter regions of TUBA1B, KIF18A, TEAD1, TAZ, YAP, TP53 and SP1 genes. ChIP-qPCR assay showed that the combined treatment decreases the binding of TEAD1 to the promoters of TUBA1B, KIF18A, TEAD1, TAZ and YAP genes in STS26T cells. The reduced binding to TP53 and SP1 promoters was also found in S462TY cells, which was further confirmed by immunoblotting. The down-regulation of these important transcri ptional factors may contribute to the vulnerability of MPNST. In summary, HDAC11 inhibitor, FT895 can potentiate the tumoricidal effect of cordycepin to suppress the MPNST cell growth, which was probably mediated by the dysfunction of hippo-signaling pathway. PMID:35261809 | PMC:PMC8899988 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Decreased RNA m6A methylation enhances the process of the epithelial mesenchymal transition and vasculogenic mimicry in glioblastoma

xlomafota13 shared this article with you from Inoreader Decreased RNA m<sup>6</sup>A methylation enhances the process of the epithelial mesenchymal transition and vasculogenic mimicry in glioblastoma Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):893-906. eCollection 2022. ABSTRACT RNA N6-methyladenosine (m6A) modification is gradually thought to be an active participant in the considerable biological processes of glioblastoma (GB), providing us with a novel insight for exploring this disease. However, the role of RNA m6A modification during the epithelial mesenchymal transition (EMT) or vasculogenic mimicry (VM) progression has not been investigated in GB. Here we performed a research to validate the impact exerted by AlkB homolog 5 (ALKBH5), one of "erasers" for RNA m6A and methyltransferase-like 3 (METTL3) which adds m6A modification to the RNAs on the progression of EMT and VM in GB. In this study, we demonstrate that the m6A levels of RNAs were reduced in GB cells and glioma tissues. Patients with high mRNA expression of ALKBH5 acquired relatively shorter median overall sur vival (OS) time, while patients with relatively high expression of MEETL3 prolonged their disease free survival. ALKBH5 enhanced GB cell proliferation and influenced cell cycle in vitro. Decreased RNA m6A methylation enhanced the progression of the EMT and VM in glioblastoma cells. ALKBH5 strengthened glioblastoma growth and enhanced the EMT and VM process of glioblastoma in vivo. Our study uncovers that RNA m6A methylation suppresses the process of EMT and VM in glioblastoma, providing a new perspective to seek for a potential therapeutic target for GB. PMID:35261810 | PMC:PMC8899976 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Significant association between serum Wisteria floribunda agglutinin-positive Mac-2-binding protein and prognosis of hepatocellular carcinoma after surgical treatment

xlomafota13 shared this article with you from Inoreader Significant association between serum Wisteria floribunda agglutinin-positive Mac-2-binding protein and prognosis of hepatocellular carcinoma after surgical treatment Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):601-614. eCollection 2022. ABSTRACT Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) is a novel marker for evaluating fibrosis and predicting the development of hepatocellular carcinoma (HCC). However, the role of WFA+-M2BP in the prognosis of HCC patients after curative surgery remains unknown. In this study, we aimed to evaluate the prognostic role of serum WFA+-M2BP in HCC patients after curative resection and liver transplantation. We enrolled 460 HCC patients (357 resection and 103 transplantation) to analyze the risk factors for HCC recurrence and patient's survival. We employed time-to-event models using univariate and multivariable Cox proportional hazards regression analyses and calculated the hazard ratios (HRs) and adjusted HRs with their corresponding 95% confidence intervals (CIs). The levels of WFA+-M2BP were 0.19 -14.51 COI (median 1.08) in patients of hepatectomy and 0.47-19.90 COI (median 6.0) in transplant patients. The levels of WFA+-M2BP in liver transplant patients is much higher than that of hepatectomy patients. Overall, liver fibrotic stage was positively correlated to WFA+-M2BP levels (P<0.0001). This study demonstrated that elevated WFA+-M2BP level (COI ≥0.75) was associated with a higher HCC recurrence rate in the resection group (P<0.001). Survival analysis showed that an elevated WFA+-M2BP level (COI ≥1.43) is associated with a higher mortality risk after surgical resection (P=0.0088) in the univariate analysis only. In liver transplant patients, WFA+-M2BP level (COI ≥3.81) did not predict HCC recurrence at all, but was associated poor survival after transplantation, with a borderline significance (P=0.0943). Serum WFA+-M2BP is a reliable marker for liver fibrosis in the present study. It is also reli able marker to predict prognosis of HCC after surgical resection. However, the prognostic role of WFA+-M2BP in HCC related transplants is equivocal, which is different from that of surgical resection. PMID:35261790 | PMC:PMC8899980 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.