Dendritic cell vaccination strategy for the treatment of acute myeloid leukemia: a systematic review.

BACKGROUND AIMS: Acute myeloid leukemia (AML) is classified as a hematologic malignancy characterized by the proliferation of immature blood cells within the bone marrow (BM), resulting in an aberrant and unregulated cellular growth. The primary therapeutic modalities for AML include chemotherapy and hematopoietic stem cell transplantation. However, it is important to note that these treatments are accompanied by important adverse effects and mortality rates. Therefore, the need for more effective treatment options seems necessary, and dendritic cell (DC) vaccine therapy can be one of these options. In this study, we aim to investigate the effectiveness of DC vaccination therapy for the management of AML. METHODS: PubMed, Scopus, ProQuest, Web of Science, and Google Scholar databases were searched for this systematic review. The articles were evaluated based on the inclusion criteria of this study and initially compared in terms of titles or abstracts. Finally, the articles related to the topic of this review were obtained in full text. The complete remission and partial remission, survival, correlative immune assays, and health-related metrics were used to evaluate this cellular immunotherapy effectiveness. The quality of the studies was assessed independently using the Cochrane risk-of-bias tools. The compiled data were input into a standard Excel spreadsheet. Each domain was evaluated as having either a "low risk," "high risk," or "unclear risk" of bias. RESULTS: Among the 3986 studies that were determined, a total of 11 correlated trials were selected for inclusion in this systematic review. DC vaccine therapy was effective in inducing complete and partial remission, and stabilization of the disease. Additionally, it was discovered that the treatment strengthened the immune system as seen by increased levels of CD4+ and CD8+ T cells, Th1 cytokines, WT1-specific T cells, and activated NK cells. CONCLUSION: We conducted a systematic review that supports the use of DC vaccine therapy as an effective treatment for AML. The therapy demonstrated potentials in achieving remission, enhancing the immune system function, and increasing overall survival. However, more studies are required to improve the methods of preparing and delivering the DC vaccine, and to confirm its long-term safety and effectiveness.

Multicenter study of some liver and heart function tests in SARS-Cov-2 patients from three ethnic groups in Iran.

The liver and cardiovascular system disorders are not common in COVID-19 patients, but the patients suffering from these complications are exposed to a higher rate of mortality and disease progression. Hepatic injuries can drive to increased levels of liver enzymes, including ALT, AST, and LDH. Abundant levels of AST, LDH, and CPK can be indicators of cardiac injuries. The current study comparise 366 individuals who are divided into COVID-19 patients and healthy individuals groups, in which we have examined hepatic and cardiac function parameters. Moreover, the clinical characteristics of the participants, ethnicities, and their difference with studied parameters were assessed. The results showed Fars individuals are more susceptible to the disease progression, including liver and heart damage. COVID-19 infection is associated with aging, which indicates that the mean age of the case group is ten years older than the control group (P < 0.001). The blood sugar in the case group (140.50) was higher than in the control group (131.66), although there was no difference between the infection and BS (P = 0.505). Similarly, the increased- mean of the ALT level in the case group (102.369) compared with the control group (68.324) resulted in no significant difference (P = 0.318). Other parameters, including CPK, LDH, and AST showed an increase in the control group values compared to the case group; however, the differences were not significant (P = 0.264, P = 0.795, P = 0.417). Considering the involvement of cardiac and hepatic organs by SARS-CoV-2, paying particular attention to the disorders of these organs through assessing the hepatic and cardiac function parameters can enhance the patient's recovery and survival. However, in this study, we not observed significant differences, except for the Fars people. There is need for further assessment of this issue.

Study on hypoxia-inducible factor and its roles in immune system.

The Hypoxia-Inducible Factor-1 (HIF-1) is a dimeric protein complex that plays a significant role in responding to low oxygen or hypoxia concentrations. Chronic inflammation is one of the immune system responses and can increase HIF expression in involved tissues through lowering the oxygen and hypoxia. The HIF factor has many critical roles in immunity, and thus, we reviewed the crucial roles of this factor in the immune system. The results showed various key roles on the immune system, including physical defenses, innate immune (neutrophils apoptosis, macrophages) and inflammatory responses (pyrexia and local heat, iron access, etc.), upregulation in response to microbial infections, cytokines expression (IL-1, IL-2, IL-6, IL-8, IL-12, IL-18, TNF, etc.), drug targeting, etc. The HIF roles in the acquired immune system include: enhance the adaptation of cells (dendritic cells) to new conditions and triggering the signal pathways. The findings of the present review demonstrated that the HIF has important roles in the immune system, including physical defense, innate immune as well as acquired immunity; therefore, it may be considered as a potent drug targeting several diseases such as cancers, infectious diseases, etc.

Varied functions of immune checkpoints during cancer metastasis.

Immune checkpoints comprise diverse receptors and ligands including costimulatory and inhibitory molecules, which play monumental roles in regulating the immune system. Immune checkpoints retain key potentials in maintaining the immune system homeostasis and hindering the malignancy development and autoimmunity. The expression of inhibitory immune checkpoints delineates an increase in a plethora of metastatic tumors and the inhibition of these immune checkpoints can be followed by promising results. On the other hand, the stimulation of costimulatory immune checkpoints can restrain the metastasis originating from diverse tumors. From the review above, key findings emerged regarding potential functions of inhibitory and costimulatory immune checkpoints targeting the metastatic cascade and point towards novel potential Achilles' heels of cancer that might be exploited therapeutically in the future.

The Impact of EGCG and RG108 on SOCS1 Promoter DNA Methylation and Expression in U937 Leukemia Cells.

BACKGROUND: The available evidence has increasingly demonstrated that a combination of genetic and epigenetic factors, such as DNA methylation, could be considered as causing leukemia. Epigenetic changes and methylation of the suppressor of the cytokine signaling 1 promoter (SOCS1) CpG region silence SOCS1 expression in cancer. In the current study, we evaluated the impact of epigallocatechin gallate (EGCG) and RG108 on SOCS1 promoter methylation and expression in U937 cells. METHODS: In the current study, U937 leukemic cells were treated with EGCG and RG108 for 12, 24, 48, and 72 h and SOCS1 promoter methylation and its expression were measured by methylation-specific PCR (MSP) and quantitative real-time PCR, respectively. RESULTS: The outcomes indicated that the SOCS1 promoter is methylated in U937 cells, and treatment of these cells with either EGCG or RG108 reduced its methylation. Moreover, we observed that SOCS1 expression was significantly upregulated in a time-dependent manner by both EGCG and RG108 in U937 cells compared with control cells. In the RG108-treated group at 12, 24, 48, and 72 h, SOCS1 expression was upregulated by 1, 4.2, 16.6, and 32.6 -fold respectively, and in the EGCG-treated group, by 0.5, 3.2, 10.8, and 22.3 -fold, respectively. CONCLUSION: Treatment with either EGCG or RG108 reduced SOCS1 promoter methylation and increased SOCS1 expression in U937 cells in a time-dependent manner, which may play a role in leukemia therapy.

The potentials of immune checkpoints for the treatment of blood malignancies.

Immune checkpoints are the regulators of the immune system, which include stimulatory and inhibitory receptors. They play substantial roles in the maintenance of immune system homeostasis and the prevention of autoimmunity and cancer. In the current review, immune checkpoints roles are surveyed in the initiation, progression, and treatment of blood malignancies. The significant roles of immune checkpoints are discussed as clinical markers in the diagnosis and prognosis of a plethora of blood malignancies and also as potential targets for the treatment of these malignancies. It could be concluded that the regulation of immune checkpoints in various blood cancers can be employed as a novel strategy to obtain effective results in leukemia treatment and introduce immune checkpoint inhibitors as sufficient weapons against blood cancers in the future.

The potential role of miR-29 in health and cancer diagnosis, prognosis, and therapy.

miR-29 family is one of the small noncoding RNAs and has a very important role in many physiologic and pathologic functions through regulating the target genes that play roles in various bioprocesses such as proliferation, survival, apoptosis, and angiogenesis. Thus, we aim to survey the potential of the miR-29 family in normal model and development and progression of malignancy in this study. In addition, the potential role of miR-29 family has been studied as the clinical marker for the diagnosis and prognosis of many cancers as the potential targets to treat cancer. Moreover, it was stated in summary that the herbal compounds can regulate miR-29 family in cancers. Therefore, regulating the expression of the miR-29 family in a variety of cancers can be a new strategy to obtain better results from cancerous patients' treatment in the future.