International journal of molecular medicine最新文献

{"title":"Clinical updates of B‑cell maturation antigen‑targeted therapy in multiple myeloma (MM) and relapsed/refractory MM (Review).","authors":"Rui Xing, Meidan Wang, Liqun Wang, Mingyue Pan, Yixi Wang, Hongwei Zhou","doi":"10.3892/ijmm.2024.5468","DOIUrl":"10.3892/ijmm.2024.5468","url":null,"abstract":"<p><p>Despite significant progress in managing multiple myeloma (MM) in recent years, certain patients still have a short duration of therapeutic response, often relapsing within 18 months. These patients typically have high‑risk genetic mutations and may show little to no response to current treatments, highlighting the need for further exploration of optimal therapeutic targets for MM. B‑cell maturation antigen (BCMA), highly expressed in mature B lymphocytes and plasma cells and upregulated in MM, is a promising therapeutic target. Various BCMA‑targeted strategies, including antibody‑drug conjugates, bispecific T‑cell engagers and chimeric antigen receptor T‑cell therapy, are under clinical evaluation to optimize efficacy and safety. This review summarizes the latest clinical updates on these strategies, highlights their effectiveness in MM and relapsed/refractory MM and provides future perspectives and recommendations for overcoming current challenges.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 2","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repositioning of aripiprazole, an anti‑psychotic drug, to sensitize the chemotherapy of pancreatic cancer.","authors":"Ye Jin Cho, Beom Seok Han, Soyeon Ko, Min Seok Park, Yun Ji Lee, Sang Eun Kim, Pureunchowon Lee, Han Gyeol Go, Shinyoung Park, Hyunho Lee, Sohee Kim, Eun-Ran Park, Kyung Hee Jung, Soon-Sun Hong","doi":"10.3892/ijmm.2024.5458","DOIUrl":"10.3892/ijmm.2024.5458","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with limited therapeutic options. Cisplatin is a primary chemotherapeutic agent utilized in combination with other drugs or radiotherapy for PDAC treatment. However, the severe side effects of cisplatin often necessitate discontinuation of therapy and drug resistance in tumor cells poses significant clinical challenges. Therefore, the development of effective therapeutic strategies is imperative. The present study investigated whether repositioning of the antipsychotic drug aripiprazole could sensitize the anticancer activity of cisplatin in pancreatic cancer at doses calculated by the combination index. The findings indicated that aripiprazole combined with cisplatin to suppress pancreatic cancer cell growth. Notably, the combination notably increased the expression of apoptosis markers, including cleaved caspase‑3, compared with cisplatin alone. Additionally, this combination effectively decreased XIAP and MCL‑1 expression via mitochondrial membrane potential change as revealed by JC‑1 assay, thereby inducing apoptosis. Furthermore, in fluid shear stress assay, the combination of aripiprazole and cisplatin notably inhibited cell adhesion and tumor spheroid formation. Mechanistically, phospho‑kinase array profiles showed that the enhanced anticancer efficacy of the combination treatment could be attributed to the inhibition of STAT3 signaling, which led to a significant reduction in tumor growth in a pancreatic cancer animal model. The results showed that the repositioning of aripiprazole inhibits cancer cell growth by blocking the STAT3 signaling pathway and effectively enhancing cisplatin‑induced apoptosis, thereby suggesting that the combination of aripiprazole and cisplatin may be a potent chemotherapeutic strategy for the treatment of pancreatic cancer.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Retracted] miR‑92a‑3p promotes the proliferation, migration and invasion of esophageal squamous cell cancer by regulating PTEN.","authors":"Xin Li, Shuilong Guo, Li Min, Qingdong Guo, Shutian Zhang","doi":"10.3892/ijmm.2024.5453","DOIUrl":"10.3892/ijmm.2024.5453","url":null,"abstract":"<p><p>Following the publication of this paper, a concerned reader drew to the Editor's attention that it appeared as if the authors had calculated the apoptotic rates erroneously. The authors were asked to provide an explanation to account for the concerns raised by the interested reader; however, they did not respond to this request submitted by the Editorial Office. Therefore, owing to the lack of responsiveness on the part of the authors, the Editor of <i>International Journal of Molecular Medicine</i> has decided that this paper should be retracted from the journal. The Editor would like to apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 44: 973‑981, 2019; DOI: 10.3892/ijmm.2019.4258].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Giant <i>Centella asiatica</i>, a novel cultivar rich in madecassoside and asiaticoside, suppresses α‑melanocyte‑stimulating hormone‑induced melanogenesis through MC1R binding.","authors":"Jiwon Seo, Chanhyeok Jeong, Seung Man Oh, Sung-Young Lee, Han Woong Park, Dae Bang Seo, Dae Sung Yoo, Woo-Jin Sim, Tae-Gyu Lim, Jung Han Yoon Park, Chang Hyung Lee, Ki Won Lee","doi":"10.3892/ijmm.2024.5454","DOIUrl":"10.3892/ijmm.2024.5454","url":null,"abstract":"<p><p>The present study investigated the anti‑melanogenesis effects of Giant <i>Centella asiatica</i> (GCA), a new cultivator of <i>Centella asiatica</i> (CA) cataloged by the Korea Forest Service in 2022, and compared its efficacy with that of traditional CA. GCA has a high yield per unit area and enhanced antioxidant properties. The anti‑melanogenic effects of GCA were investigated using B16F10 melanoma cells and a 3D human skin‑equivalent model. Key molecular mechanisms were elucidated through western blotting, cAMP assays and molecular docking studies. Focus was addressed on the effect of GCA on skin whitening by comparing the ability of a GCA extract to inhibit melanin production in B16F10 melanoma cells and a 3D human skin‑equivalent model to that of CA. The results showed that the GCA extracts more effectively reduced melanin production, which was attributed to their higher content of two active components, madecassoside and asiaticoside. Further investigation revealed that GCA primarily inhibited melanogenesis through the PKA‑cAMP response element‑binding (CREB)‑microphthalmia‑associated transcription factor (MITF) axis, a key regulatory pathway in melanin synthesis. Notably, the present study, to the best of our knowledge, is the first to demonstrate that madecassoside and asiaticoside, the two principal compounds in GCA, directly bound to MC1R, which contributed to the significant skin‑whitening effects. Moreover, GCA reduced melanin production in a 3D human skin‑equivalent model, showing efficacy within a complex skin environment. These results demonstrated the superior effectiveness of GCA to that of CA for skin anti‑melanogenesis, indicating its potential as a promising natural material for targeting pigmentation disorders.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin ameliorates senescence and promotes osteogenesis of BMSCs by suppressing the repetitive element‑triggered RNA sensing pathway.","authors":"Yutong Sun, Chunyang Wang, Liling Wen, Zihang Ling, Juan Xia, Bin Cheng, Jianmin Peng","doi":"10.3892/ijmm.2024.5445","DOIUrl":"10.3892/ijmm.2024.5445","url":null,"abstract":"<p><p>Cell senescence impedes the self‑renewal and osteogenic capacity of bone marrow mesenchymal stem cells (BMSCs), thus limiting their application in tissue regeneration. The present study aimed to elucidate the role and mechanism of repetitive element (RE) activation in BMSC senescence and osteogenesis, as well as the intervention effect of quercetin. In an H2O2‑induced BMSC senescence model, quercetin treatment alleviated senescence as shown by a decrease in senescence‑associated β‑galactosidase (SA‑β‑gal)‑positive cell ratio, increased colony formation ability and decreased mRNA expression of p21 and senescence‑associated secretory phenotype genes. DNA damage response marker γ‑H2AX increased in senescent BMSCs, while expression of epigenetic markers methylation histone H3 Lys9, heterochromatin protein 1α and heterochromatin‑related nuclear membrane protein lamina‑associated polypeptide 2 decreased. Quercetin rescued these alterations, indicating its ability to ameliorate senescence by stabilizing heterochromatin structure where REs are primarily suppressed. Transcriptional activation of REs accompanied by accumulation of cytoplasmic double‑stranded (ds)RNA, as well as triggering of the RNA sensor retinoic acid‑inducible gene I (RIG‑I) receptor pathway in H2O2‑induced senescent BMSCs were shown. Similarly, quercetin treatment inhibited these responses. Additionally, RIG‑I knockdown led to a decreased number of SA‑β‑gal‑positive cells, confirming its functional impact on senescence. Induction of senescence or administration of dsRNA analogue significantly hindered the osteogenic capacity of BMSCs, while quercetin treatment or RIG‑I knockdown reversed the decline in osteogenic function. The findings of the current study demonstrated that quercetin inhibited the activation of REs and the RIG‑I RNA sensing pathway via epigenetic regulation, thereby alleviating the senescence of BMSCs and promoting osteogenesis.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TP53 mutations in cancer: Molecular features and therapeutic opportunities (Review).","authors":"Maria Lina Tornesello","doi":"10.3892/ijmm.2024.5448","DOIUrl":"10.3892/ijmm.2024.5448","url":null,"abstract":"<p><p>The tumour suppressor factor p53 plays an essential role in regulating numerous cellular processes, including the cell cycle, DNA repair, apoptosis, autophagy, cell metabolism and immune response. TP53 is the most commonly mutated gene in human cancers. These mutations are primarily non‑synonymous changes that produce mutant p53 proteins characterized by loss of function, a dominant negative effect on p53 tetramerisation and gain of function (GOF). GOF mutations not only disrupt the tumour‑suppressive activities of p53 but also endow the mutant proteins with new oncogenic properties. Recent studies analysing different pathogenic features of mutant p53 in cancer‑derived cell lines have demonstrated that restoring wild‑type p53, rather than removing GOF mutations, reduces cancer cell growth. These findings suggest that therapeutic strategies for reactivating wild‑type p53 function in cancer cells may bring a greater benefit than approaches halting mutant p53. This approach could involve the use of small molecules, gene therapy and other methods to re‑establish wild‑type p53 activity. This review describes the complexity of the biological activities of different p53 mutants and summarizes the current therapeutic approaches to restore p53 function.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay between lncRNAs and the PI3K/AKT signaling pathway in the progression of digestive system neoplasms (Review).","authors":"Xiaoyu Zhang, Lei Shi, Mengzhen Xing, Chunjing Li, Fengjun Ma, Yuning Ma, Yuxia Ma","doi":"10.3892/ijmm.2024.5456","DOIUrl":"10.3892/ijmm.2024.5456","url":null,"abstract":"<p><p>Long non‑coding RNA (lncRNA) is a class of non‑coding RNA molecules located in the cytoplasm or nucleus, which can regulate chromosome structure and function by interacting with DNA, RNA, proteins and other molecules; binding to mRNA bases in a complementary manner, affecting the splicing, stabilization, translation and degradation of mRNA; acting as competing endogenous RNA competitively binds to microRNAs to regulate gene expression and participate in the regulation of various vital activities of the body. The PI3K/AKT signalling pathway plays a key role in numerous biological and cellular processes, such as cell proliferation, invasion, migration and angiogenesis. It has been found that the lncRNA/PI3K/AKT axis regulates the expression of cancer‑related genes and thus tumour progression. The abnormal regulation of lncRNA expression in the lncRNA/PI3K/AKT axis is clearly associated with clinicopathological features and plays an important role in regulating biological functions. In the present review, the expression and biological functions of PI3K/AKT‑related lncRNAs both <i>in vitro</i> and <i>in vivo</i> over recent years, were comprehensively summarized and analyzed. Their correlation with clinicopathological features was also evaluated, with the objective of furnishing a solid theoretical foundation for clinical diagnosis and the monitoring of efficacy in digestive system neoplasms. The present review aimed to provide a comprehensive overview of the expression and biological functions of PI3K/AKT‑related lncRNAs in digestive system neoplasms and to assess their correlation with clinicopathological features. This endeavor seeks to establish a solid theoretical foundation for the clinical diagnosis and efficacy monitoring of digestive system tumors.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An emerging double‑edged sword role of ferroptosis in cardiovascular disease (Review).","authors":"Sirun Qin, Can Zhu, Chenyang Chen, Zhe Sheng, Yu Cao","doi":"10.3892/ijmm.2024.5457","DOIUrl":"10.3892/ijmm.2024.5457","url":null,"abstract":"<p><p>The pathophysiology of cardiovascular disease (CVD) is complex and presents a serious threat to human health. Cardiomyocyte loss serves a pivotal role in both the onset and progression of CVD. Among various forms of programmed cell death, ferroptosis, along with apoptosis, autophagy and pyroptosis, is closely linked to the advancement of CVD. Ferroptosis, a mechanism of cell death, is driven by the buildup of oxidized lipids and excess iron. This pathway is modulated by lipid, amino acid and iron metabolism. Key characteristics of ferroptosis include disrupted iron homeostasis, increased peroxidation of polyunsaturated fatty acids due to reactive oxygen species, decreased glutathione levels and inactivation of glutathione peroxidase 4. Treatments targeting ferroptosis could potentially prevent or alleviate CVD by inhibiting the ferroptosis pathway. Ferroptosis is integral to the pathogenesis of several types of CVD and inhibiting its occurrence in cardiomyocytes could be a promising therapeutic strategy for the future treatment of CVD. The present review provided an in‑depth analysis of advancements in understanding the mechanisms underlying ferroptosis. The present manuscript summarized the interplay between ferroptosis and CVDs, highlighting its dual roles in these conditions. Additionally, potential therapeutic targets within the ferroptosis pathway were discussed, alongside the current limitations and future directions of these novel treatment strategies. The present review may offer novel insights into preventive and therapeutic approaches for CVDs.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Corrigendum] A regulation loop between Nrf1α and MRTF‑A controls migration and invasion in MDA‑MB‑231 breast cancer cells.","authors":"Yao Xu, Ying Luo, Chen Liang, Weibing Xing, Tongcun Zhang","doi":"10.3892/ijmm.2024.5442","DOIUrl":"10.3892/ijmm.2024.5442","url":null,"abstract":"<p><p>Subsequently to the publication of this article, an interested reader drew to the authors' attention that the Control and Nrf1α data panels in Fig. 1G on p. 2463 contained overlapping data, such that these data, which were intended to show the results from differently performed experiments, had apparently been derived from the same original source. Upon examining their original data, the authors realized that the image for the Control experiment was selected incorrectly for this figure. In rectifying this error, the authors have chosen to show the data from one of their repeated experiments for Fig. 1G, and the revised version of this figure is shown on the next page. They can confirm that the replacement of these data in this corrigendum does not significantly affect the conclusions reported in the study. The authors are grateful to the Editor of <i>International Journal of Molecular Medicine</i> for allowing them the opportunity to publish this corrigendum, and wish to apologize to readership for any inconvenience caused. [International Journal of Molecular Medicine 42: 2459‑2468, 2018; DOI: 10.3892/ijmm.2018.3816].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in predicting breast cancer driver mutations: Tools for precision oncology (Review).","authors":"Wenhui Hao, Barani Kumar Rajendran, Tingting Cui, Jiayi Sun, Yingchun Zhao, Thirunavukkarasu Palaniyandi, Masilamani Selvam","doi":"10.3892/ijmm.2024.5447","DOIUrl":"10.3892/ijmm.2024.5447","url":null,"abstract":"<p><p>In the modern era of medicine, prognosis and treatment, options for a number of cancer types including breast cancer have been improved by the identification of cancer‑specific biomarkers. The availability of high‑throughput sequencing and analysis platforms, the growth of publicly available cancer databases and molecular and histological profiling facilitate the development of new drugs through a precision medicine approach. However, only a fraction of patients with breast cancer with few actionable mutations typically benefit from the precision medicine approach. In the present review, the current development in breast cancer driver gene identification, actionable breast cancer mutations, as well as the available therapeutic options, challenges and applications of breast precision oncology are systematically described. Breast cancer driver mutation‑based precision oncology helps to screen key drivers involved in disease development and progression, drug sensitivity and the genes responsible for drug resistance. Advances in precision oncology will provide more targeted therapeutic options for patients with breast cancer, improving disease‑free survival and potentially leading to significant successes in breast cancer treatment in the near future. Identification of driver mutations has allowed new targeted therapeutic approaches in combination with standard chemo‑ and immunotherapies in breast cancer. Developing new driver mutation identification strategies will help to define new therapeutic targets and improve the overall and disease‑free survival of patients with breast cancer through efficient medicine.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}