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The Regulatory Effect of ERK1 Pathway in the DNA Hypomethylation of MRL/lpr Mice
Miaoxuan Luo,
Shanshan Wei,
Xiangbin Mi,
Tangde Zhang,
Wu Zhang
Issue:
Volume 9, Issue 3, September 2021
Pages:
41-46
Received:
17 July 2021
Accepted:
9 August 2021
Published:
18 August 2021
Abstract: Background: Defective ERK1 activity may regulate the DNA hypomethylation in T cells of lupus mice. Aims: To investigate the function of ERK1 in regulating DNA hypomethylation and explore the potential molecular mechanisms involved in lupus mice. Methods: CD4+T cells were isolated from MRL/lpr and BALB/c mice, activated in vitro in the presence or absence of 5-azacytidine (5-Aza) (a DNA methyltransferase inhibitor)/U0126 (a selective inhibitor of the ERK signaling pathway) respectively. The positive rate of CD4+T cell was measured by flow cytometry, and expression levels of CD70, ERK1, DNA transferase 1 (DNMT1) were estimated by RT-PCR and Western blot. The methylated DNA is detected using the Capture and Detection antibodies, then quantified colorimetrically. Results: The expression level of p-ERK1 in MRL/lpr mice was significantly lower than healthy control (P<0.05); Meanwhile, down regulation of DNMT1 and DNA hypomethylation were found in MRL/lpr mice T cells. In contrary, the expression levels of CD70 increased when compared with healthy control (P<0.05). The same changes were seen in healthy CD4+T cells treated with U0126. Conclusions: DNA hypomethylation regulating mechanisms in lupus T cells were associated with ERK1 signal pathway. U0126 could inhibit ERK1 signal transduction pathway in normal T cells, and induce DNA hypomethylation by regulating the expression of methylation sensitive gene CD70.
Abstract: Background: Defective ERK1 activity may regulate the DNA hypomethylation in T cells of lupus mice. Aims: To investigate the function of ERK1 in regulating DNA hypomethylation and explore the potential molecular mechanisms involved in lupus mice. Methods: CD4+T cells were isolated from MRL/lpr and BALB/c mice, activated in vitro in the presence or a...
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Immunohistochemical Expression of MMP-2 in Pancreatic Carcinoma and Chronic Pancreatitis
Afaf Taha El-Nashar,
Eman Muhammad Salah Muhammad,
Mohammed Hamdy Sayed,
Said Abuel-kheer Mohammed
Issue:
Volume 9, Issue 3, September 2021
Pages:
47-53
Received:
6 March 2021
Accepted:
16 March 2021
Published:
19 August 2021
Abstract: Introduction: Matrix metalloproteinase (MMP)-2 is a member of MMPs family which is zinc-dependent endopeptidases that degrade all components of ECM and vascular basement membrane. MMPs are closely involved in tumor invasion and metastasis. Aim of the work: is to evaluate the immune-expression and clinical significance of MMPs molecule in patients with pancreatic carcinoma. Materials and Methods: A total of 25 pancreatic carcinomas were evaluated for expression of MMP-2 by immunohistochemical technique. The expression was evaluated. The study included 24/25 cases of PDAC and 1/25 acinar cell carcinoma. PDAC included 5/24 cases of well differentiated, 16/24 cases of moderately differentiated, 3/24 cases of poorly differentiated adenocarcinoma. Results: Pancreatic carcinoma specimens showed positive cytoplasmic MMP-2 staining with high expression in 88% of studied specimens as their IRS ranged from 6/9 to 9/9 with high extent and intensity. There was a statistically significant relationship between MMP-2 expression and high grade in PDAC (p<0.024). Conclusion: MMP-2 was expressed in PDAC and not in pancreatitis cases. The expression of MMP-2 was correlated with high histological grade and poor prognosis in PDAC.
Abstract: Introduction: Matrix metalloproteinase (MMP)-2 is a member of MMPs family which is zinc-dependent endopeptidases that degrade all components of ECM and vascular basement membrane. MMPs are closely involved in tumor invasion and metastasis. Aim of the work: is to evaluate the immune-expression and clinical significance of MMPs molecule in patients w...
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A Case of Recurrence/Refractory Mediastinal Hodgkin's Lymphoma Relapsed After Allogeneic Hematopoietic Stem Cell Transplantation: Immunotherapy Brings Hope
Jiaxin Wang,
Jiaxiong Tan,
Yuhong Lu
Issue:
Volume 9, Issue 3, September 2021
Pages:
54-58
Received:
3 September 2021
Accepted:
17 September 2021
Published:
26 September 2021
Abstract: Hodgkin lymphoma (HL), is a B-cell lymphoma. HL is a common hematological malignancy, mostly seen in young and middle-aged people. According to NCCN guidelines, common treatment options include ABVD, BEACOPP, StandfordV, etc. Most HL have a good prognosis and even can be cured. However, some Refractory / Recurrent (R/R) HL, continue to progress during treatment or even relapse after the completion of a complete chemotherapy course 3 months. At this time, the best treatment for R/R HL is high-dose chemotherapy / Autologous Hematopoietic Stem Cell Transplantation (HDC/HSCT). This paper reports a case of Recurrence/Refractory (R/R) mediastinal Hodgkin's lymphoma that relapsed after Allogeneic Hematopoietic Stem Cell Transplantation. After receiving a variety of treatments, including chemotherapy, radiotherapy, autologous hematopoietic stem cell transplantation and so on, no long-term sustained remission was achieved. Traditional chemotherapy regimen has not brought ideal therapeutic effect to patients, but the rapid development of immunotherapy in recent years has brought new hope to patients. Finally sustained remission was achieved under the treatment of Brentuximab Vedotin combined with PD-1 inhibitor. This paper combined with the literature reports and discussed the clinical characteristics, treatment process and related experience and thinking methods of immunotherapy related to PD-1 inhibitors in this refractory and easy-to-relapse case. To provide more clinical data for the application of immunotherapy in R/R HL.
Abstract: Hodgkin lymphoma (HL), is a B-cell lymphoma. HL is a common hematological malignancy, mostly seen in young and middle-aged people. According to NCCN guidelines, common treatment options include ABVD, BEACOPP, StandfordV, etc. Most HL have a good prognosis and even can be cured. However, some Refractory / Recurrent (R/R) HL, continue to progress dur...
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Potential Treatment for Multiple Myeloma: Immune Checkpoint Inhibitors
Jiaxin Wang,
Jiaxiong Tan,
Yuhong Lu
Issue:
Volume 9, Issue 3, September 2021
Pages:
59-67
Received:
3 September 2021
Accepted:
17 September 2021
Published:
26 September 2021
Abstract: Multiple myeloma (MM) is a malignant disease in which monoclonal plasma cells proliferate abnormally. The poor prognosis of MM is always closely related to the immunosuppression of T cells. Restore the immune function of suppressed T cells may reverse the immunodeficiency in the MM microenvironment and improve prognosis. In recent years, immunosuppressive receptors such as programmed cell death receptor-1 (PD-1), T cells immunoglobulin and ITIM domain (TIGIT), Lymphocyte-Activation Gene-3 (LAG-3), T cell immunoglobulin and mucin domain–containing molecule 3 (Tim-3), Leukocyte immunoglobulin-like receptor B1 (LILRB1) and Cytotoxic T- lymphocyte antigen 4 (CTLA-4) have been discovered playing a key role in the tumor immunodeficiency microenvironment. For patients with solid tumors and some leukemia, immunotherapy targeting such receptors can significantly improve the T cells immunodeficiency. However, similar positive results were not found in MM patients, which is related to the complex immunosuppressive mechanism. At present, the understanding of immunosuppressive receptors in MM is insufficient. In this review, this paper summarized part of the studies on PD-1, TCLA-4, Tim-3, TIGIT and other popular immunosuppressive receptors in MM, in order to attract more attention, and in-depth research on the immunotherapy also to promote the immunotherapy of MM from basic research to clinical transformation as soon as possible.
Abstract: Multiple myeloma (MM) is a malignant disease in which monoclonal plasma cells proliferate abnormally. The poor prognosis of MM is always closely related to the immunosuppression of T cells. Restore the immune function of suppressed T cells may reverse the immunodeficiency in the MM microenvironment and improve prognosis. In recent years, immunosupp...
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