JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

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KRAS mutation promotes the colonization of Fusobacterium nucleatum in colorectal cancer by down-regulating SERTAD4 KRAS 基因突变通过下调 SERTAD4 促进核酸镰刀菌在结直肠癌中的定植。
IF 5.3
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-27 DOI: 10.1111/jcmm.70182
Yizhen Chen, Yuanyuan Zheng, Shaolin Liu
{"title":"KRAS mutation promotes the colonization of Fusobacterium nucleatum in colorectal cancer by down-regulating SERTAD4","authors":"Yizhen Chen,&nbsp;Yuanyuan Zheng,&nbsp;Shaolin Liu","doi":"10.1111/jcmm.70182","DOIUrl":"10.1111/jcmm.70182","url":null,"abstract":"<p>This study explores and verifies potential molecular targets through which KRAS mutations regulate the colonization of Fusobacterium nucleatum (FN) in colorectal cancer (CRC). This study combined multiple bioinformatics methods and biological assays. Through The Cancer Genome Atlas, Gene Expression Omnibus, Human Protein Atlas, immunohistochemistry, and co-culture assays, we further confirmed the differential expression of SERTAD4 in CRC. We delved deeper into examining how expression of SERTAD4 is linked with immune cell infiltration and the enrichment of potential pathways. Lastly, through bacterial phenotypic assays, we validated the function of SERTAD4. As a molecule associated with KRAS mutations and FN infection, the expression levels of SERTAD4 were downregulated in CRC. The diagnostic efficacy of SERTAD4 for CRC is not inferior to that of CEA. Low expression of SERTAD4 is associated with poorer overall survival in CRC. Correlation analysis found that increased expression of SERTAD4 is associated with various immune cell infiltrations and immune checkpoint genes. Finally, bacterial adhesion and invasion assays verify that SERTAD4 inhibits the adhesion and invasion abilities of FN in CRC. This study demonstrates that SERTAD4 exerts a protective role in CRC by inhibiting the colonization of FN.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Old disease—New reflections: Gaucher, immunity, and inflammation 老疾病-新思考:戈谢病、免疫和炎症
IF 5.3
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-27 DOI: 10.1111/jcmm.70087
Can Veysel Şoroğlu, Ezgi Gizem Berkay
{"title":"Old disease—New reflections: Gaucher, immunity, and inflammation","authors":"Can Veysel Şoroğlu,&nbsp;Ezgi Gizem Berkay","doi":"10.1111/jcmm.70087","DOIUrl":"10.1111/jcmm.70087","url":null,"abstract":"<p>Gaucher disease (GD) is the most common lysosomal storage disease. It is a multisystemic metabolic disease caused by <i>GBA</i> pathogenic mutations. Although the general symptoms have been known for a long time, new treatment possibilities, the detection of different biomarkers, and innovations in diagnosis and follow-up have paved the way for further studies. Recent studies have shown that the immune system has become an essential factor associated with disease progression. The role of Gaucher cells in the disease is well characterized. In addition to phagocytic macrophage cells, lymphocytes, complement system, and inflammatory pathway elements are also implicated in GD as they were shown to be the underlying factors causing associated pathologies such as Parkinson's. In this article, the relationship between the GD and the immune system has been examined and reviewed in light of new findings.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Puerarin alleviates apoptosis and inflammation in kidney stone cells via the PI3K/AKT pathway: Network pharmacology and experimental verification 葛根素通过 PI3K/AKT 通路缓解肾结石细胞的凋亡和炎症:网络药理学与实验验证
IF 5.3
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-27 DOI: 10.1111/jcmm.70180
Yuexian Xu, Hu Liang, Xike Mao, Zhenyu Song, Xudong Shen, Defeng Ge, Yang Chen, Bingbing Hou, Zongyao Hao
{"title":"Puerarin alleviates apoptosis and inflammation in kidney stone cells via the PI3K/AKT pathway: Network pharmacology and experimental verification","authors":"Yuexian Xu,&nbsp;Hu Liang,&nbsp;Xike Mao,&nbsp;Zhenyu Song,&nbsp;Xudong Shen,&nbsp;Defeng Ge,&nbsp;Yang Chen,&nbsp;Bingbing Hou,&nbsp;Zongyao Hao","doi":"10.1111/jcmm.70180","DOIUrl":"10.1111/jcmm.70180","url":null,"abstract":"<p>Puerarin(PUE), an isoflavonoid extracted from Pueraria root, has anti-apoptotic effects. The objective of this research is to examine the impact of PUE on renal apoptosis and inflammation resulting from renal calculi and to elucidate its mechanism. The approach of network pharmacology and molecular docking was employed to discover potential targets and pathways of PUE. An animal model of calcium oxalate crystal deposition by intraperitoneal injection of glyoxylate and a model of COM-induced human renal tubular epithelial cells (HK2) were used to investigate the pharmacological mechanisms of PUE against apoptosis and inflammation. We used haematoxylin–eosin (H&amp;E) and Periodic Acid-Schiff staining (PAS) to assess the effect of PUE on crystal deposition and damage. The mechanism of PUE was elucidated and validated using Western blotting, histology and immunohistochemical staining. Network pharmacology findings indicated that the PI3K/AKT pathway plays a crucial role in PUE. We experimentally demonstrate that PUE alleviated COM-induced changes in apoptotic proteins, increased inflammatory indicators and changes in oxidative stress-related indicators in HK2 cells by activating the PI3K/AKT pathway, reduced serum creatinine and urea nitrogen levels in mice caused by CaOx, alleviated crystal deposition and damage, and alleviated apoptosis, oxidative stress and inflammation. Puerarin attenuates renal apoptosis and inflammation caused by kidney stones through the PI3K/AKT pathway.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multi-omics analysis reveals BZW1's regulation of EMT via the Wnt pathway in lung adenocarcinoma 多组学分析揭示 BZW1 通过 Wnt 通路调控肺腺癌的 EMT
IF 5.3
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-27 DOI: 10.1111/jcmm.70163
Wei Lai, Zhou Ping, Yun Chen, Junrong Wang, Yuyan Liu, Shishi Zou, Jieweng Wang, Tianyu Zhang, Wei Ren, Wei Wang
{"title":"Multi-omics analysis reveals BZW1's regulation of EMT via the Wnt pathway in lung adenocarcinoma","authors":"Wei Lai,&nbsp;Zhou Ping,&nbsp;Yun Chen,&nbsp;Junrong Wang,&nbsp;Yuyan Liu,&nbsp;Shishi Zou,&nbsp;Jieweng Wang,&nbsp;Tianyu Zhang,&nbsp;Wei Ren,&nbsp;Wei Wang","doi":"10.1111/jcmm.70163","DOIUrl":"10.1111/jcmm.70163","url":null,"abstract":"<p>Exploring the role of novel cancer gene BZW1 in lung adenocarcinoma (LUAD) and unveiling associated signalling pathways. Firstly, we conducted a pan-cancer analysis of BZW1 using multiple databases. Subsequently, leveraging single-cell data from LUAD, we successfully uncovered potential oncological processes associated with BZW1 and further validated them through experimentation. Simultaneously, we continued to investigate the potential molecular mechanisms underlying the oncological processes mediated by BZW1. Additionally, we employed various machine learning algorithms to construct prognostic models concerning BZW1 and the epithelial-mesenchymal transition (EMT) process. Our research firstly demonstrated the elevated expression of BZW1 in various cancer cells. Leveraging single-cell data from LUAD, we identified that BZW1 regulates the occurrence of EMT in LUAD, a phenomenon validated across multiple LUAD cell lines. Moreover, we further discovered that BZW1 regulates LUAD's EMT process through the Wnt/β-catenin signalling pathway. Lastly, we successfully constructed prognostic models using BZW1-related genes and EMT genes.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Caffeic acid inhibits Staphylococcus aureus-induced endometritis through regulating AMPKα/mTOR/HIF-1α signalling pathway 咖啡酸通过调节AMPKα/mTOR/HIF-1α信号通路抑制金黄色葡萄球菌诱发的子宫内膜炎
IF 5.3
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-27 DOI: 10.1111/jcmm.70175
Lu Cao, Junbao Liu, Cong Ye, Yubo Hu, Rui Qin
{"title":"Caffeic acid inhibits Staphylococcus aureus-induced endometritis through regulating AMPKα/mTOR/HIF-1α signalling pathway","authors":"Lu Cao,&nbsp;Junbao Liu,&nbsp;Cong Ye,&nbsp;Yubo Hu,&nbsp;Rui Qin","doi":"10.1111/jcmm.70175","DOIUrl":"10.1111/jcmm.70175","url":null,"abstract":"<p>Endometritis is mostly caused by childbirth or postpartum uterine infection. It is one of the important reasons leading to female infertility. Caffeic acid (CA) and its derivatives are widely found in some foods and traditional Chinese medicine, and have biological activities such as antioxidant, free radical scavenging, anti-inflammatory, and anti-infection. In this study, we aimed to explore the effect of CA on <i>Staphylococcus aureus</i>-induced endometritis. The contents of TNF-α and IL-1β were detected by ELISA in <i>S. aureus</i>-induced endometritis model. Western blot assay was used to detect the expression of AMPKα/mTOR/HIF-1α pathway related proteins and GPX4 expression. In addition, the concentrations of MDA, GSH, and iron were tested by the assay kits. Compared with the model group, CA treatment significantly alleviated <i>S. aureus</i>-induced uterine injury, MPO activity, the contents of inflammatory factors TNF-α and IL-1β, and NF-κB activation. Meanwhile, CA significantly inhibited <i>S. aureus</i>-induced ferroptosis, as confirmed by decreased MDA and iron concentration and up-regulated GPX4 expression and GSH level. Furthermore, CA attenuated <i>S. aureus</i>-induced HIF-1α and phosphorylated mTOR expression and increased phosphorylated AMPK expression. In conclusion, CA inhibits inflammation and ferroptosis by regulating AMPKα/mTOR/HIF-1α signalling pathway to alleviate <i>S. aureus</i>-induced endometritis in mice.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Macrophage polarization-related gene signature for risk stratification and prognosis of survival in gliomas 用于胶质瘤生存风险分层和预后的巨噬细胞极化相关基因特征。
IF 5.3
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-24 DOI: 10.1111/jcmm.70000
Weiming Zhong, Kaifen Xiong, Shuwang Li, Chuntao Li
{"title":"Macrophage polarization-related gene signature for risk stratification and prognosis of survival in gliomas","authors":"Weiming Zhong,&nbsp;Kaifen Xiong,&nbsp;Shuwang Li,&nbsp;Chuntao Li","doi":"10.1111/jcmm.70000","DOIUrl":"10.1111/jcmm.70000","url":null,"abstract":"<p>Macrophage polarization plays an essential role in tumour immune cell infiltration and tumour growth. In this study, we selected a series of genes distinguishing between M1 and M2 macrophages and explored their prognostic value in gliomas. A total of 170 genes were included in our study. The CGGA database was used as the training cohort and the TCGA database as the validation cohort. The biological processes and functions were identified by GO and KEGG analysis. Kaplan–Meier analysis was used to compare survival differences between groups. Importantly, we built a risk score model using Cox regression analysis based on the CGGA and verified it in the TCGA database and our sequencing data. Patients with gliomas in the high-risk group were associated with high pathologic grade, IDH WT status, MGMT promoter unmethylation, 1p19q non-codeletion and prone to have a poor outcome. GEPIA results revealed that CD300C, CNRIP1 and MYO1F are the most related genes of immune infiltrations. The differential expression of these genes between low-grade gliomas and glioblastomas was confirmed by q-RT-PCR. Macrophage polarization-related gene signatures can predict the malignancy and outcome of patients with gliomas and might act as a promising target for glioma immunotherapy in the future.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitogen-activated protein kinase kinase kinase 1 facilitates the temozolomide resistance and migration of GBM via the MEK/ERK signalling 丝裂原活化蛋白激酶激酶1通过MEK/ERK信号传导促进替莫唑胺的抗药性和GBM的迁移。
IF 5.3
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-23 DOI: 10.1111/jcmm.70173
Sicheng Wu, Senrui Xue, Yuchen Tang, Wenyu Zhao, Maojin Zheng, Zhixuan Cheng, Xin Hu, Jinmin Sun, Jing Ren
{"title":"Mitogen-activated protein kinase kinase kinase 1 facilitates the temozolomide resistance and migration of GBM via the MEK/ERK signalling","authors":"Sicheng Wu,&nbsp;Senrui Xue,&nbsp;Yuchen Tang,&nbsp;Wenyu Zhao,&nbsp;Maojin Zheng,&nbsp;Zhixuan Cheng,&nbsp;Xin Hu,&nbsp;Jinmin Sun,&nbsp;Jing Ren","doi":"10.1111/jcmm.70173","DOIUrl":"10.1111/jcmm.70173","url":null,"abstract":"<p>Mitogen-Activated Protein Kinase Kinase Kinase 1 (MAP3K1) is overexpressed in gliomas; however, its clinical significance, biological functions, and underlying molecular mechanisms remain unclear. Abnormal overexpression of MAP3K1 in glioma is strongly associated with unfavourable clinicopathological characteristics and disease progression. MAP3K1 could potentially serve as a reliable diagnostic and prognostic biomarker for glioma. MAP3K1 silencing suppressed the migration but had no effect on the proliferation and cell death of Glioblastoma Multiforme (GBM) cells. MAP3K1 knockdown exacerbated the temozolomide (TMZ) induced inhibition of glioma cell proliferation and death of GBM cells. In addition, MAP3K1 knockdown combined with TMZ treatment significantly inhibited the growth and increased cell death in organoids derived from GBM patients. MAP3K1 knockdown reversed TMZ resistance of GBM in intracranial glioma model. In terms of molecular mechanisms, the phosphorylation level of ERK was significantly decreased by MAP3K1 silencing. No significant change in the JNK pathway was found in MAP3K1-silenced GBM cells. Inhibition of ERK phosphorylation suppressed the migration and enhanced the TMZ sensibility of GBM cells. MAP3K1 was correlated with the immune infiltration in glioma. MAP3K1 could facilitate the migration and TMZ resistance of GBM cells through MEK/ERK signalling.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PLXNB1/SEMA4D signals mediate interactions between malignant epithelial and immune cells to promote colorectal cancer liver metastasis PLXNB1/SEMA4D信号介导恶性上皮细胞和免疫细胞之间的相互作用,促进结直肠癌肝转移。
IF 5.3
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-23 DOI: 10.1111/jcmm.70142
Zixue Xuan, Yuan Zhang, Dan Li, Kai Wang, Ping Huang, Jiana Shi
{"title":"PLXNB1/SEMA4D signals mediate interactions between malignant epithelial and immune cells to promote colorectal cancer liver metastasis","authors":"Zixue Xuan,&nbsp;Yuan Zhang,&nbsp;Dan Li,&nbsp;Kai Wang,&nbsp;Ping Huang,&nbsp;Jiana Shi","doi":"10.1111/jcmm.70142","DOIUrl":"10.1111/jcmm.70142","url":null,"abstract":"<p>Distal metastases result from metastatic microenvironment and tumour epithelial cell interactions, the cellular heterogeneity of primary colorectal cancer (CRC) and liver metastases (LM) was evaluated by integrating single-cell sequencing data, and the collected gene expression data from metastatic epithelial cell subsets was used to construct a prognostic model and to identify intercellular receptor-ligand interactions between epithelial and immune cells in CRC and LM. Multiplex immunofluorescence staining, and in vitro wound healing, cell migration and cell apoptosis assays were performed to further explore the biological relevance of identified potential regulatory molecules. In this study, approximately 17 epithelial cell subtypes were detected, with Epi-11 cells being highly expressed in LM tissues compared with CRC samples. Furthermore, patients with high expression of the metastasis-related genetic profile of Epi-11 had a poorer prognosis. By predicting receptor–ligand interactions, Epi-11 cells were found to interact more with myeloid and T/natural killer cells in LM tissues when compared to primary CRC samples, which was mediated by the PLXNB1/SEMA4D axis. In addition, high <i>SEMA4D</i> expression was correlated with decreased overall survival of patients with CRC, whereas <i>PLXNB1</i> was not. <i>SEMA4D</i> knockdown prevented the migration and promoted the apoptosis of HCT116 cells in vitro. In summary, Epi-11 cells, an important subset of epithelial cells, may drive the LM of CRC and act by crosstalk with immune cells through the PLXNB1/SEMA4D signalling axis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single low-dose decitabine as frontline therapy of acute myeloid leukaemia, with venetoclax salvage 将单一低剂量地西他滨作为急性髓性白血病的前线疗法,并辅以 Venetoclax 挽救治疗。
IF 5.3
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-22 DOI: 10.1111/jcmm.18592
Ciprian Jitaru, Mareike Cathrina Peters, Lovisha Aggarwal, Anamaria Bancos, Adrian Bogdan Tigu, Diana Cenariu, Cristina Selicean, Sergiu Pasca, Vlad Moisoiu, Petra Rotariu, Maria Santa, Sabina Iluta, Rares Drula, David Kegyes, Aranka Kurtus, Mihnea Zdrenghea, Lukasz Gondek, Ciprian Tomuleasa, Gabriel Ghiaur
{"title":"Single low-dose decitabine as frontline therapy of acute myeloid leukaemia, with venetoclax salvage","authors":"Ciprian Jitaru,&nbsp;Mareike Cathrina Peters,&nbsp;Lovisha Aggarwal,&nbsp;Anamaria Bancos,&nbsp;Adrian Bogdan Tigu,&nbsp;Diana Cenariu,&nbsp;Cristina Selicean,&nbsp;Sergiu Pasca,&nbsp;Vlad Moisoiu,&nbsp;Petra Rotariu,&nbsp;Maria Santa,&nbsp;Sabina Iluta,&nbsp;Rares Drula,&nbsp;David Kegyes,&nbsp;Aranka Kurtus,&nbsp;Mihnea Zdrenghea,&nbsp;Lukasz Gondek,&nbsp;Ciprian Tomuleasa,&nbsp;Gabriel Ghiaur","doi":"10.1111/jcmm.18592","DOIUrl":"10.1111/jcmm.18592","url":null,"abstract":"&lt;p&gt;The introduction of the combination therapy hypomethylating agents (HMA) with venetoclax established a new standard of care for patients with de novo AML who are unfit for intensive cytotoxic treatment.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Standard dose HMA (pulse-cycled administration for 5–7 days every 4 weeks) used as a single agent or in combination exerts indiscriminate cytotoxic effects on both tumour cells and healthy haematopoietic tissue&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; Historically, the dosing schedule of HMA treatments was initially established based on the maximum tolerated dose (decitabine [DEC]: 1500–2500 mg/m&lt;sup&gt;2&lt;/sup&gt;), proving impractical in AML patients due to prolonged myelosuppression.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Empiric down titration yielded clinically effective doses of HMAs with acceptable side effects (DEC: 20 mg/kg/day).&lt;span&gt;&lt;sup&gt;5, 6&lt;/sup&gt;&lt;/span&gt; As an epigenetic modulator at non-cytotoxic doses (0.1–0.2 mg/kg/day), DEC incorporates into newly synthesized DNA and depletes the chromatin-modifying enzyme DNA methyltransferase 1 (DNMT1). Hypomethylation of tumour cell-specific dysregulated DNA methylation patterns leads to changes in gene expression, restoring cell differentiation in favour of cell proliferation.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; Simultaneously, normal haematopoietic stem cells are stimulated to self-renew,&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; while committed progenitors are prompted to differentiate, thus limiting toxic effects on healthy haematopoietic cells.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; Higher frequency administrations of HMAs at lower concentrations might decrease treatment-related complications, thereby providing a reasonable treatment strategy for extremely unfit patients with AML.&lt;/p&gt;&lt;p&gt;For in vitro studies, seven AML cell lines were used (MV4-11, TF-1, THP1, MOLM-14, OCI-AML3, OCI-AML5 and UCSD-AML1). Cells were cultured in RPMI Medium 1640 (Gibco) supplemented with 10% heat-inactivated fetal bovine serum, 2 mM L-glutamine (Gibco) and 100 units/mL Pen/Strep (Gibco) at 37°C, 5% CO2. Cell viability post-drug treatment was evaluated using the CellTiter 96 AQueous One Solution kit (Promega). Cells were seeded in 96-well plates and treated with 0.5 μM DEC and venetoclax (VEN) starting from 10 μM up to eight 10-fold dilutions, or DEC alone, using seven ten-fold dilutions starting from 5 μM. In all drug experiments, corresponding cell-free reactions were established for background correction. Triplicate measurements were conducted for all dose–response experiments. The absorbance values were read using CLARIOstar Plus Microplate Reader. Data were analysed using MS Excel and visualized using GraphPad Prism. The combination index was calculated using the Bliss independence formula to assess drug synergism.&lt;span&gt;&lt;sup&gt;13&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Patients were deemed ‘unfit for intensive therapy’ clinically by the treating physician. The study protocol was approved by the ethics committee of the Oncology Institute ‘Prof. Dr. Ion Chiricuţă’ Cluj-Napoca, R","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The roles of G protein-coupled receptor kinase 2 in renal diseases G 蛋白偶联受体激酶 2 在肾脏疾病中的作用。
IF 5.3
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-22 DOI: 10.1111/jcmm.70154
Jiayin Du, Xiaoyan Wu, Lihua Ni
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