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Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To investigate the clinical significance, functional role and potential downstream mechanism of USP5 in acute myeloid leukemia (AML).
OBJECTIVE
To investigate the clinical significance, functional role and potential downstream mechanism of USP5 in acute myeloid leukemia (AML).
METHODS
The expression of in AML and normal tissues and its correlation with patients' survival were analyzed based on TCGA database. was knocked down and overexpressed in Jurkat and HL-60 cells using lentivirus. USP5 mRNA and protein expression were detected by RT-qPCR and Western blot, respectively. Cell proliferation and growth were measured by CCK-8 and methylcellulose colony-forming assay. Flow cytometry was used to analyze cell cycle and apoptosis.
RESULTS
was highly expression in AML compared with normal tissues. Up-regulation of was negatively correlated with the survival of AML patients. knockdown and overexpression inhibited and promoted the proliferation and colony growth of AML cells, respectively. Cell cycle arrest and apoptosis were induced in knockdown Jurkat and HL-60 cells. Furthermore, knockdown inhibited the phosphrylation of AKT, mTOR and 4EBP1.
CONCLUSION
Overexpression of predicts poor survival of AML patients. Targeting USP5 suppresses AKT/mTOR/4EBP1 signaling and reduces the proliferation and growth of AML cells.
Topics: Humans; Leukemia, Myeloid, Acute; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; Cell Proliferation; HL-60 Cells; Apoptosis; Adaptor Proteins, Signal Transducing; Cell Cycle Proteins; Jurkat Cells; Ubiquitin-Specific Proteases; Clinical Relevance
PubMed: 38926952
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.004 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To investigate the effect of expression regulated by miR-21 on proliferation and apoptosis of acute myeloid leukemia cells.
OBJECTIVE
To investigate the effect of expression regulated by miR-21 on proliferation and apoptosis of acute myeloid leukemia cells.
METHODS
Seventy patients with AML admitted to our hospital from January 2019 to July 2022 were selected, while 30 patients with iron deficiency anemia were selected as the control group. Bone marrow mononuclear cells (BMMNCs) of the patients were obtained using Ficoll density gradient centrifugation. RT-qPCR was used to determine the expression levels of and mRNA in BMMNCs. Mimics-miR-21, mimics-NC, inhibitor-miR-21, inhibitor-NC and NC were transfected into HL-60 cells using liposome-mediated transfection technology. CCK-8 method was used to determine the activity of transfected HL-60 cells after treatment with cytarabine. The apoptosis rate of HL-60 transfected cells was determined by TUNEL method. The expression of mRNA in HL-60 cells transfected with inhibitor-miR-21 was determined by RT-qPCR.
RESULTS
The relative expression levels of and mRNA in BMMNCs of AML patients were significantly higher than those of controls (both < 0.05). After HL-60 cells were treated with cytarabine, both the cell activity of inhibitor-miR-21 group and mimics-miR-21 group decreased significantly with the increase of cytarabine concentration (both < 0.05). However, at each concentration point of cytarabine, the cell activity of inhibitor-miR-21 group was lower than that of control group ( < 0.05), while mimics-miR-21 group was higher than control group ( < 0.05). After HL-60 cells were treated with cytarabine, the apoptosis rate of inhibitor-miR-21 group was significantly increased ( < 0.05), while that of mimics-miR-21 group was significantly decreased ( < 0.05). After HL-60 cells were treated with inhibitor-miR-21, the relative expression of mRNA decreased significantly ( < 0.05).
CONCLUSION
miR-21 is highly expressed in AML patients, which may promote the apoptosis of AML cells by inhibiting the expression of .
Topics: Humans; MicroRNAs; Leukemia, Myeloid, Acute; Apoptosis; Cell Proliferation; HL-60 Cells; Transfection; Cytarabine
PubMed: 38926950
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.002 -
European Journal of Pharmacology Jun 2024Pancreatic ductal adenocarcinoma (PDAC) remains a dreadful disease with poor prognosis. While the prognosis of colorectal carcinoma (CRC) is better than that of PDAC, it... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) remains a dreadful disease with poor prognosis. While the prognosis of colorectal carcinoma (CRC) is better than that of PDAC, it still is the second-leading cause of cancer deaths worldwide. Recently, a (methyl)lanthionine-stabilized, highly receptor-specific agonist of galanin subtype 2 (GAL2) receptor inhibited the growth of GAL2 receptor-expressing patient-derived xenografts (PDX) of pancreatic cancer. Furthermore, a lanthionine-constrained agonist of angiotensin II type 2 (AT) receptor inhibited PDX of colorectal cancer in mice. Stimulation of GAL2 receptor may modulate immune surveillance and inhibits PDAC via cell cycle inhibition and apoptosis. Consistent with GAL2 receptor-mediated tumor inhibition, for PDAC, survival is much higher for patients with high GAL2 receptor expression. Importantly, a (methyl)lanthionine-stabilized GAL2 receptor-specific agonist enhances expression of GAL2 receptor, not only in PDAC-PDX but also in healthy tissue indicating therapeutic and preventive potentials for GAL2 receptor agonists. ATR is interacting with four tumor suppressor proteins, Src homology phosphatase 1, Src homology phosphatase 2, Promyelocytic Leukemia Zinc Finger protein and Microtuble-Associated Scaffold Protein1, the latter also known as Angiotensin-II type 2 receptor-Interacting Protein. Pathways linked to these tumor suppressor proteins may enhance immune surveillance, prevent carcinogenesis, counter proliferation and stimulate apoptosis. Taken together, current data are prompting the hypothesis of a prophylactic treatment option with stable, specific and safe agonists of GAL2 receptor and AT receptor to prevent the emergence of pancreatic and colorectal cancer in individuals at risk.
PubMed: 38925290
DOI: 10.1016/j.ejphar.2024.176772 -
Hematology Reports Jun 2024Acute promyelocytic leukemia is a rare form of acute myeloid leukemia in which immature promyelocytes abnormally proliferate in the bone marrow. In most cases, the...
Acute promyelocytic leukemia is a rare form of acute myeloid leukemia in which immature promyelocytes abnormally proliferate in the bone marrow. In most cases, the disease is characterised by the translocation t(15;17) (q24;q21), which causes the formation of PML::RARA, an oncogenic fusion protein responsible for blocking myeloid differentiation and survival advantage. Here, we present a case of acute promyelocytic leukemia with two unusual features: basophilic differentiation and a three-way translocation involving chromosomes 12, 15 and 17. In the few cases reported, basophilic differentiation was associated with a poor prognosis. In contrast, our patient responded promptly to the standard treatment with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) and obtained complete remission. To our knowledge, this is the first report of basophilic acute promyelocytic leukemia with the three-way translocation t(12;17;15) (p13; q24;q21).
PubMed: 38921185
DOI: 10.3390/hematolrep16020037 -
Surgical Case Reports Jun 2024Gastrointestinal mucormycosis is a rapidly progressing and often fatal disease, predominantly affecting immunocompromised patients. Surgical intervention, in addition to...
BACKGROUND
Gastrointestinal mucormycosis is a rapidly progressing and often fatal disease, predominantly affecting immunocompromised patients. Surgical intervention, in addition to antifungal therapy, is essential. Herein, we describe the successful management of appendiceal mucormycosis in a patient with acute promyelocytic leukemia through rapid surgical intervention and antifungal therapy.
CASE PRESENTATION
A 29-year-old woman underwent autologous peripheral blood stem cell transplantation for acute promyelocytic leukemia (APL). Subsequently, her condition relapsed, and remission induction therapy was initiated. During the immunosuppressive period, she developed a fever and severe abdominal pain. Computed tomography revealed severe edema of the ileum, cecum, and ascending colon. Despite receiving multiple antibiotics, antivirals, and antifungals, her condition showed no improvement. Consequently, she underwent exploratory laparotomy, with no bowel perforation noted, revealing severe inflammation in the ileum, cecum, and ascending colon, as well as appendiceal necrosis. Appendectomy was performed, and histopathological analysis revealed hyphae in the vessels and layers of the appendiceal wall, suggestive of mucormycosis. The patient was diagnosed with appendiceal mucormycosis, and liposomal amphotericin B was administered. Subsequent monitoring showed no recurrence of mucormycosis. Genetic analysis of the resected tissue revealed Rhizopus microspores as the causative agent.
CONCLUSIONS
Rapid surgical intervention and antifungal drug administration proved successful in managing appendiceal mucormycosis in a patient with APL. Early recognition and aggressive surgical intervention are imperative to improve outcomes in such patients.
PubMed: 38916715
DOI: 10.1186/s40792-024-01958-y -
Expert Opinion on Drug Delivery Jun 2024Arsenicals have a special place in the history of human health, acting both as poison and medicine. Having been used to treat a variety of diseases in the past, the... (Review)
Review
INTRODUCTION
Arsenicals have a special place in the history of human health, acting both as poison and medicine. Having been used to treat a variety of diseases in the past, the success of arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL) in the last century marked its use as a drug in modern medicine. To expand their role against cancer, there have been clinical uses of arsenicals worldwide and progress in the development of drug delivery for various malignancies, especially solid tumors.
AREAS COVERED
In this review, conducted on Google Scholar [1977-2024], we start with various forms of arsenicals, highlighting the well-known ATO. The mechanism of action of arsenicals in cancer therapy is then overviewed. A summary of the research progress in developing new delivery approaches (e.g. polymers, inorganic frameworks, and biomacromolecules) in recent years is provided, addressing the challenges and opportunities in treating various malignant tumors.
EXPERT OPINION
Reducing toxicity and enhancing therapeutic efficacy are guidelines for designing and developing new arsenicals and drug delivery systems. They have shown potential in the fight against cancer and emerging pathogens. New technologies and strategies can help us harness the potency of arsenicals and make better products.
PubMed: 38913024
DOI: 10.1080/17425247.2024.2372363 -
Patient Preference and Adherence 2024Acute leukemia is a cancer of the white blood cells which progresses rapidly and aggressively. There are two types: acute lymphoblastic leukemia (ALL) and acute myeloid...
BACKGROUND
Acute leukemia is a cancer of the white blood cells which progresses rapidly and aggressively. There are two types: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). The latter has a rare subtype: acute promyelocytic leukemia (APL). For some patients, following first-line treatment, remission is not achieved ("refractory disease"), and for others the leukemia returns after achieving remission ("relapse"). For these individuals, outcomes are typically poor. It is, therefore, important to understand patients' treatment priorities in this context.
METHODS
Building upon formative qualitative research, an online survey containing a discrete choice experiment (DCE) was designed to explore patients' treatment preferences in the relapsed/refractory setting. The DCE attributes were mode of administration; quality of life during treatment; chance of response; duration of response; and quality of life during response. Each respondent completed twelve scenarios containing two hypothetical treatments. Participants were eligible if they lived in the United Kingdom and had a diagnosis of acute leukemia. The data were analysed using a latent class model.
RESULTS
A total of 95 patients completed the survey. The latent class analysis identified two classes. For both, chance of response was the most important attribute. For class 1, every attribute was important, whereas for class 2, the only important attributes were quality of life (during treatment and response) and chance of response. A greater proportion of respondents would fall into class 1 overall, and those with ALL or APL and those more recently diagnosed were more likely to be in class 2.
CONCLUSION
Our results indicate that patients are strongly concerned about the chance of response, as well as quality of life (to a lesser extent), when faced with different treatment options in the relapsed/refractory setting. However, there is significant preference heterogeneity within the patient population, and other treatment characteristics also matter to many.
PubMed: 38911590
DOI: 10.2147/PPA.S442530 -
Biology Direct Jun 2024Most patients with acute myeloid leukemia (AML) eventually develop drug resistance, leading to a poor prognosis. Dysregulated long gene non coding RNAs (lincRNAs) have...
BACKGROUND
Most patients with acute myeloid leukemia (AML) eventually develop drug resistance, leading to a poor prognosis. Dysregulated long gene non coding RNAs (lincRNAs) have been implicated in chemoresistance in AML. Unfortunately, the effects of lincRNAs which participate in regulating the Adriamycin (ADR) resistance in AML cells remain unclear. Thus, the purpose of this study is to determine LINC00987 function in ADR-resistant AML.
METHODS
In this study, ADR-resistant cells were constructed. LINC00987, miRNAs, and HMGA2 mRNA expression were measured by qRT-PCR. P-GP, BCRP, and HMGA2 protein were measured by Western blot. The proliferation was analyzed by MTS and calculated IC50. Soft agar colony formation assay and TUNEL staining were used to analyze cell colony formation and apoptosis. Xenograft tumor experiment was used to analyze the xenograft tumor growth of ADR-resistant AML.
RESULTS
We found that higher expression of LINC00987 was observed in AML patients and associated with poor overall survival in AML patients. LINC00987 expression was increased in ADR-resistant AML cells, including ADR/MOLM13 and ADR/HL-60 cells. LINC00987 downregulation reduces ADR resistance in ADR/MOLM13 and ADR/HL-60 cells in vitro and in vivo, while LINC00987 overexpression enhanced ADR resistance in MOLM13 and HL-60 cells. Additionally, LINC00987 functions as a competing endogenous RNA for miR-4458 to affect ADR resistance in ADR/MOLM13 and ADR/HL-60 cells. HMGA2 is a target of miR-4458. LINC00987 knockdown and miR-4458 overexpression reduced HMGA2 expression. HMGA2 overexpression enhanced ADR resistance, which reversed the function of LINC00987 silencing in suppressing ADR resistance of ADR/MOLM13 and ADR/HL-60 cells.
CONCLUSIONS
Downregulation of LINC00987 weakens ADR resistance by releasing miR-4458 to deplete HMGA2 in ADR/MOLM13 and ADR/HL-60. Therefore, LINC00987 may act as the therapeutic target for treating chemoresistant AML.
Topics: Leukemia, Myeloid, Acute; Humans; HMGA2 Protein; MicroRNAs; Drug Resistance, Neoplasm; Doxorubicin; RNA, Long Noncoding; Mice; Animals; Cell Line, Tumor; HL-60 Cells; Gene Silencing; Apoptosis; Cell Proliferation; Female
PubMed: 38910243
DOI: 10.1186/s13062-024-00490-1 -
Cell Communication and Signaling : CCS Jun 2024Pseudomonas aeruginosa (PA) is an opportunistic pathogen that can cause sight threatening infections in the eye and fatal infections in the cystic fibrosis airway....
BACKGROUND
Pseudomonas aeruginosa (PA) is an opportunistic pathogen that can cause sight threatening infections in the eye and fatal infections in the cystic fibrosis airway. Extracellular vesicles (EVs) are released by host cells during infection and by the bacteria themselves; however, there are no studies on the composition and functional role of host-derived EVs during PA infection of the eye or lung. Here we investigated the composition and capacity of EVs released by PA infected epithelial cells to modulate innate immune responses in host cells.
METHODS
Human telomerase immortalized corneal epithelial cells (hTCEpi) cells and human telomerase immortalized bronchial epithelial cells (HBECs) were treated with a standard invasive test strain of Pseudomonas aeruginosa, PAO1, for 6 h. Host derived EVs were isolated by qEV size exclusion chromatography. EV proteomic profiles during infection were compared using mass spectrometry and functional studies were carried out using hTCEpi cells, HBECs, differentiated neutrophil-like HL-60 cells, and primary human neutrophils isolated from peripheral blood.
RESULTS
EVs released from PA infected corneal epithelial cells increased pro-inflammatory cytokine production in naïve corneal epithelial cells and induced neutrophil chemotaxis independent of cytokine production. The EVs released from PA infected bronchial epithelial cells were also chemotactic although they failed to induce cytokine secretion from naïve HBECs. At the proteomic level, EVs derived from PA infected corneal epithelial cells exhibited lower complexity compared to bronchial epithelial cells, with the latter having reduced protein expression compared to the non-infected control.
CONCLUSIONS
This is the first study to comprehensively profile EVs released by corneal and bronchial epithelial cells during Pseudomonas infection. Together, these findings show that EVs released by PA infected corneal and bronchial epithelial cells function as potent mediators of neutrophil migration, contributing to the exuberant neutrophil response that occurs during infection in these tissues.
Topics: Humans; Pseudomonas aeruginosa; Extracellular Vesicles; Pseudomonas Infections; Neutrophils; Epithelial Cells; Cytokines; HL-60 Cells
PubMed: 38907250
DOI: 10.1186/s12964-024-01609-7 -
EJHaem Jun 2024
PubMed: 38895076
DOI: 10.1002/jha2.887