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.

Characteristics and Cytotoxic Effects of Nano-Liposomal Paclitaxel on Gastric Cancer Cells.

OBJECTIVE: Addressing both the initial treatment response and subsequent paclitaxel resistance is a pivotal concern. Nano drug delivery, an emerging approach, presents a cutting-edge alternative to conventional chemotherapy. METHODS: This investigation synthesized PEGylated nanoparticles (NPs) via the Reverse Phase Evaporation technique for liposomal NPs. Characteristics such as zeta potential, size, drug release and polydispersity index (PDI) were subjected to evaluation. Subsequently, cytotoxicity assays were conducted on gastric cancer cells (AGS) following 24 and 48-hour incubation periods. RESULTS: In this study, the liposomal NPs had a zeta potential of -22 mV and a particle size of 285 nm. The Entrapment efficiency was determined as 41% that occurred physically. Additionally, the liposomal NPs demonstrated a high drug retention rate (39% remained after 72 hours), and they exhibited significantly increased cytotoxicity compared to the free drug, confirming their effectiveness as a suitable carrier for paclitaxel during both incubation periods (P<0.05). CONCLUSION: These findings collectively advocate the potential of liposomal NPs as promising contenders for effective nano-drug application in propelling chemotherapy forward.

Overexpression of the GClnc1 as a Diagnostic Biomarker in Gastric Cancer Patients and its Link with H. Pylori Infection.

BACKGROUND: Gastric cancer (GC) is a complicated multifactorial neoplasm with a high fatality and prevalence rate around the globe that required the discovery of many unknown mechanisms involved in its inception and progression. The aim of this project was to investigate the alterations of GClnc1 expression in cancerous tissues relative to marginal non-cancerous tissues of patients with GC and its association with clinicopathological features. METHODS: In this research, the expression level of GClnc1 was assessed using the qRT-PCR. For this, 80 pairs of cancerous and marginal non-cancerous GC samples tissues were gathered. Then RNA isolation and cDNA synthesis were carried out. Eventually, the difference of GClnc1 expression levels in tumor tissue relative to marginal non-tumor tissue specimens of GC patients and its association with pathological characteristics, as well as biomarker's performance of GClnc1, was investigated. RESULTS: Expression data examination of GClnc1 indicates increased expression in GC tumor tissues relative to marginal non-cancerous tissues (p < 0.0001). GClnc1 overexpression was significantly linked with pathological features of patients with lymph node metastasis (p = 0.037) and H. pylori infection (p = 0.029). Based on ROC analysis, the GClnc1 as a biomarker has AUC, sensitivity%, and specificity% of 0.8228, 90%, and 61.67%, respec-tively (p < 0.0001). CONCLUSIONS: Due to the GClnc1 increased expression in tumor tissues of GC patients, our research proposed that GClnc1 may be involved in the promotion and development of GC cells as a novel oncogene. Besides, in the molecular targeted therapies of GC patients, GClnc1 can be considered as a potential biomarker.

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.

Alpha7 Nicotinic Acetylcholine Receptor Mediates Nicotine-induced Apoptosis and Cell Cycle Arrest of Hepatocellular Carcinoma HepG2 Cells.

Purpose: The cytotoxic properties upon treatment with nicotine have been reported in several studies, but the underlying mechanisms remain not fully defined. The alpha7 nicotinic acetylcholine receptor (α7nAChR) is one of the important nicotinic receptors, which nicotine partly by binding to this receptor exerts its effects. The current study aimed to investigates the influences of nicotine on cellular proliferative and apoptotic activities and tried to determine the involvement of α7nAChR in these functions. Methods: Human hepatocellular carcinoma (HepG2) cell line was used to determine the individual or combined effects of treatments with nicotine (10 µM) and specific siRNA (100 nM) targeting α7nAChR expression. The MTT assay, DAPI staining assay, and flow cytometry assay were applied to measure the cell viability, apoptosis and cell cycle progression of the cells, respectively. In addition, the changes in the mRNA level of the genes were assessed by qRT-PCR. Results: Compared to control groups, the cells treated with nicotine exhibited significant dosedependent decreases in cell viability (log IC50 = -5.12±0.15). Furthermore, nicotine induced apoptosis and cell cycle arrest especially at G2/M Phase. The qRT-PCR revealed that nicotine increased the mRNA levels of α7nAChR as well as caspase-3 and suppressed the expression of cyclin B1. Treatment with α7-siRNA abolished these effects of nicotine. Conclusion: These experiments determined that upregulation of α7nAChR by nicotine inhibits HepG2 cells proliferation and induces their apoptosis. These effects blocked by treatment with α7-siRNA, which indicates the involvement of α7nAChR pathways in these processes.

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.