Expert Opinion on Therapeutic Targets最新文献_第6页

Tumor cells-derived extracellular vesicles carry circ_0064516 competitively inhibit microRNA-6805-3p and promote cervical cancer angiogenesis and tumor growth. 肿瘤细胞衍生的细胞外囊泡携带的circ_0064516能竞争性抑制microRNA-6805-3p，促进宫颈癌血管生成和肿瘤生长。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-01-01 Epub Date: 2024-03-11 DOI: 10.1080/14728222.2024.2306353

Yujue Wang, Yao Xie, Xue Wang, Nian Yang, Zhao Wu, Xun Zhang

{"title":"Tumor cells-derived extracellular vesicles carry circ_0064516 competitively inhibit microRNA-6805-3p and promote cervical cancer angiogenesis and tumor growth.","authors":"Yujue Wang, Yao Xie, Xue Wang, Nian Yang, Zhao Wu, Xun Zhang","doi":"10.1080/14728222.2024.2306353","DOIUrl":"10.1080/14728222.2024.2306353","url":null,"abstract":"Background: The current study tried to elucidate the regulatory role of tumor cell-derived exosomes (Exos)-circ_0064516 in angiogenesis and growth of cervical cancer.Research design and methods: Related cirRNAs and downstream target genes were identified through bioinformatics analysis. Exos were isolated from cervical cancer cell line CaSki, followed by co-cultured with human umbilical vein endothelial cells (HUVECs). Then, the roles of circ_0064516, miR-6805-3p, and MAPK1 in migration and angiogenesis of HUVECs were assayed. Furthermore, xenografted tumors were transplanted into nude mice for in vivo validation.Results: In vitro assay validated highly expressed circ_0064516 in cervical cancer cells. Tumor cell-derived Exos carried circ_0064516 to HUVECs. circ_0064516 increased MAPK1 expression by binding to miR-6805-3p, thus enhancing migration and angiogenesis. Exos containing circ_0064516 also promoted tumorigenesis of cervical cancer cells in nude mice.Conclusions: We confirmed the oncogenic role of tumor cell-derived Exos carrying circ_0064516 in cervical cancer progression through miR-6805-3p/MAPK1.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cytokines of the interleukin-6 family as emerging targets in inflammatory bowel disease. 作为炎症性肠病新靶点的白细胞介素-6 家族细胞因子。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-01-01 Epub Date: 2024-01-23 DOI: 10.1080/14728222.2024.2306341

Christoph Garbers, Juliane Lokau

{"title":"Cytokines of the interleukin-6 family as emerging targets in inflammatory bowel disease.","authors":"Christoph Garbers, Juliane Lokau","doi":"10.1080/14728222.2024.2306341","DOIUrl":"10.1080/14728222.2024.2306341","url":null,"abstract":"Introduction: Inflammatory bowel disease (IBD) is an umbrella term that includes different chronic inflammatory diseases of the gastrointestinal tract, most commonly Crohn's disease and ulcerative colitis. IBD affects more than 6 million people worldwide and constitutes not only a debilitating disease for the patients, but also a significant factor for society due to costs for health care and reduced working capacity. Despite the introduction of biologicals for the treatment of IBD, the identification of novel targets that could lead to novel therapeutics is still needed.Areas covered: In this review, we summarize current knowledge about the interleukin-6 family of cytokines as potential therapeutic targets for improving the therapy of patients with IBD. We discuss cytokines like IL-6 itself for which therapeutics such as inhibitory monoclonal antibodies have already entered the clinics, but also focus on other family members whose therapeutic potential has not been explored yet.Expert opinion: The different cytokines of the IL-6 family offer multiple therapeutic targets that can potentially be used to treat patients with inflammatory bowel disease, but unwanted side effects like inhibition of epithelial regeneration have to be considered.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Myricetin, a natural inhibitor of CD147, increases sensitivity of cisplatin in ovarian cancer. CD147的天然抑制剂杨梅素能提高卵巢癌患者对顺铂的敏感性。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-01-01 Epub Date: 2024-01-23 DOI: 10.1080/14728222.2024.2306345

Lin Chen, Tian Fan, Miao Wang, Chun-Yu Zhu, Wang-You Feng, Yu Li, Hong Yang

{"title":"Myricetin, a natural inhibitor of CD147, increases sensitivity of cisplatin in ovarian cancer.","authors":"Lin Chen, Tian Fan, Miao Wang, Chun-Yu Zhu, Wang-You Feng, Yu Li, Hong Yang","doi":"10.1080/14728222.2024.2306345","DOIUrl":"10.1080/14728222.2024.2306345","url":null,"abstract":"Background: Ovarian cancer (OC) is the most lethal gynecological tumor, but it currently lacks effective therapeutic targets. CD147, which is overexpressed in OC, plays a crucial role in promoting malignant progression and is associated with poor prognosis in patients. Therefore, CD147 has been identified as a potential therapeutic target. However, there is a limited amount of research on the development of CD147 inhibitors.Methods: Surface plasmon resonance (SPR) assay and virtual molecular docking analysis were performed to identify potential natural compounds targeting CD147. The anti‑tumor effects of myricetin were evaluated using various assays, including CCK8, Alkaline comet, immunofluorescence and xenograft mouse models. The underlying mechanism was investigated through western blot analysis and lentivirus short hairpin RNA (LV-shRNA) transfection.Results: Myricetin, a flavonoid commonly found in plants, was discovered to be a potent inhibitor of CD147. Our findings demonstrated that myricetin exhibited a strong affinity for CD147 and down-regulated the protein level of CD147 by facilitating its proteasome-dependent degradation. Additionally, we observed synergistic antitumor effects of myricetin and cisplatin both in vivo and in vitro. Mechanistically, myricetin suppressed the expression of FOXM1 and its downstream DNA damage response (DDR) genes E×O1and BRIP1, thereby enhancing the DDR induced by cisplatin.Conclusion: Our data demonstrate that myricetin, a natural inhibitor of CD147, may have clinical utility in the treatment of OC due to its ability to increase genomic toxicity when combined with cisplatin.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New therapeutic targets for endometrial cancer: a glimpse into the preclinical sphere. 子宫内膜癌的新治疗靶点：临床前一瞥。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-01-01 Epub Date: 2024-02-12 DOI: 10.1080/14728222.2024.2316739

Ilan Bruchim, Ilaria Capasso, Ariel Polonsky, Shilhav Meisel, Vanda Salutari, Haim Werner, Domenica Lorusso, Giovanni Scambia, Francesco Fanfani

{"title":"New therapeutic targets for endometrial cancer: a glimpse into the preclinical sphere.","authors":"Ilan Bruchim, Ilaria Capasso, Ariel Polonsky, Shilhav Meisel, Vanda Salutari, Haim Werner, Domenica Lorusso, Giovanni Scambia, Francesco Fanfani","doi":"10.1080/14728222.2024.2316739","DOIUrl":"10.1080/14728222.2024.2316739","url":null,"abstract":"Introduction: Endometrial cancer (EC) is the only gynecologic malignancy showing increasing trends in incidence and mortality. While standard treatment has been effective primarily for early-stage EC, precision medicine with tailored therapy has revolutionized the management of this disease. Genome sequencing analyses have identified four sub-types of EC. Treatments for primary and metastatic disease can now be tailored more accurately to achieve better oncologic results.Areas covered: This review provides an overview of the most relevant and updated evidence in the literature regarding EC molecular analysis and its role in risk classification, prognostication, and guidance for tailored and target therapies in early and advanced/metastatic stages. In addition, it provides updated information on optimal surgical management based on molecular classification and highlights key advances and future strategies.Expert opinion: EC molecular analysis yields the potential of tailoring adjuvant treatment by escalating or deescalating therapy, as shown for POLE-mutated and p53-mutated tumors. Moreover, the expression of specific molecular signatures offers the possibility to employ novel target therapies, such as immune-checkpoint inhibitors that have demonstrated a significant benefit on prognosis. New treatment guidelines are still being established, and ongoing studies are exploring the potential prognostic role of further sub-stratifications of the four molecular classes and treatment options.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of the P2Y12 receptor on thrombus formation and evolution in therapeutic strategies. P2Y12 受体在血栓形成和治疗策略演变中的作用。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-01-01 Epub Date: 2024-02-06 DOI: 10.1080/14728222.2024.2315017

Mattia Galli, Dominick J Angiolillo

引用次数: 0

Epigenetic determinants in soft tissue sarcomas: molecular mechanisms and therapeutic targets. 软组织肉瘤中的表观遗传决定因素：分子机制和治疗目标。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-01-01 Epub Date: 2024-01-26 DOI: 10.1080/14728222.2024.2306344

Alessandra Merlini, Martina Rabino, Silvia Brusco, Valeria Pavese, Debora Masci, Dario Sangiolo, Paolo Bironzo, Giorgio Vittorio Scagliotti, Silvia Novello, Lorenzo D'Ambrosio

{"title":"Epigenetic determinants in soft tissue sarcomas: molecular mechanisms and therapeutic targets.","authors":"Alessandra Merlini, Martina Rabino, Silvia Brusco, Valeria Pavese, Debora Masci, Dario Sangiolo, Paolo Bironzo, Giorgio Vittorio Scagliotti, Silvia Novello, Lorenzo D'Ambrosio","doi":"10.1080/14728222.2024.2306344","DOIUrl":"10.1080/14728222.2024.2306344","url":null,"abstract":"Introduction: Soft tissue sarcomas are a group of rare, mesenchymal tumors characterized by dismal prognosis in advanced/metastatic stages. Knowledge of their molecular determinants is still rather limited. However, in recent years, epigenetic regulation - the modification of gene expression/function without DNA sequence variation - has emerged as a key player both in sarcomagenesis and sarcoma progression.Areas covered: Herein, we describe and review the main epigenetic mechanisms involved in chromatin remodeling and their role as disease drivers in different soft tissue sarcoma histotypes, focusing on epithelioid sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumors. Focusing on chromatin-remodeling complexes, we provide an in-depth on the role of BAF complex alterations in these soft tissue sarcoma histotypes. In parallel, we highlight current state-of-the-art and future perspectives in the development of rational, innovative treatments leveraging on epigenetic dysregulation in soft tissue sarcomas.Expert opinion: Therapeutic options for metastatic/advanced sarcomas are to date very limited and largely represented by cytotoxic agents, with only modest results. In the continuous attempt to find novel targets and innovative, effective drugs, epigenetic mechanisms represent an emerging and promising field of research, especially for malignant peripheral nerve sheath tumors, epithelioid and synovial sarcoma.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Kv1.3 in the spotlight for treating immune diseases. Kv1.3 成为治疗免疫疾病的焦点。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-01-01 Epub Date: 2024-02-07 DOI: 10.1080/14728222.2024.2315021

María Navarro-Pérez, Jesusa Capera, Anna Benavente-Garcia, Silvia Cassinelli, Magalí Colomer-Molera, Antonio Felipe

{"title":"Kv1.3 in the spotlight for treating immune diseases.","authors":"María Navarro-Pérez, Jesusa Capera, Anna Benavente-Garcia, Silvia Cassinelli, Magalí Colomer-Molera, Antonio Felipe","doi":"10.1080/14728222.2024.2315021","DOIUrl":"10.1080/14728222.2024.2315021","url":null,"abstract":"Introduction: Kv1.3 is the main voltage-gated potassium channel of leukocytes from both the innate and adaptive immune systems. Channel function is required for common processes such as Ca2+ signaling but also for cell-specific events. In this context, alterations in Kv1.3 are associated with multiple immune disorders. Excessive channel activity correlates with numerous autoimmune diseases, while reduced currents result in increased cancer prevalence and immunodeficiencies.Areas covered: This review offers a general view of the role of Kv1.3 in every type of leukocyte. Moreover, diseases stemming from dysregulations of the channel are detailed, as well as current advances in their therapeutic research.Expert opinion: Kv1.3 arises as a potential immune target in a variety of diseases. Several lines of research focused on channel modulation have yielded positive results. However, among the great variety of specific channel blockers, only one has reached clinical trials. Future investigations should focus on developing simpler administration routes for channel inhibitors to facilitate their entrance into clinical trials. Prospective Kv1.3-based treatments will ensure powerful therapies while minimizing undesired side effects.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Powering down the mitochondrial LonP1 protease: a novel strategy for anticancer therapeutics. 抑制线粒体 LonP1 蛋白酶：抗癌疗法的新策略。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-01-01 Epub Date: 2023-12-29 DOI: 10.1080/14728222.2023.2298358

Rahul Shetty, Roberto Noland, Ghata Nandi, Carolyn K Suzuki

{"title":"Powering down the mitochondrial LonP1 protease: a novel strategy for anticancer therapeutics.","authors":"Rahul Shetty, Roberto Noland, Ghata Nandi, Carolyn K Suzuki","doi":"10.1080/14728222.2023.2298358","DOIUrl":"10.1080/14728222.2023.2298358","url":null,"abstract":"Introduction: Mitochondrial LonP1 is an ATP-powered protease that also functions as an ATP-dependent chaperone. LonP1 plays a pivotal role in regulating mitochondrial proteostasis, metabolism and cell stress responses. Cancer cells exploit the functions of LonP1 to combat oncogenic stressors such as hypoxia, proteotoxicity, and oxidative stress, and to reprogram energy metabolism enabling cancer cell proliferation, chemoresistance, and metastasis.Areas covered: LonP1 has emerged as a potential target for anti-cancer therapeutics. We review how cytoprotective functions of LonP1 can be leveraged by cancer cells to support oncogenic growth, proliferation, and survival. We also offer insights into small molecule inhibitors that target LonP1 by two distinct mechanisms: competitive inhibition of its protease activity and allosteric inhibition of its ATPase activity, both of which are crucial for its protease and chaperone functions.Expert opinion: We highlight advantages of identifying specific, high-affinity allosteric inhibitors blocking the ATPase activity of LonP1. The future discovery of such inhibitors has potential application either alone or in conjunction with other anticancer agents, presenting an innovative approach and target for cancer therapeutics.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10939840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial permeability transition pore: a snapshot of a therapeutic target. 线粒体通透性转换孔：治疗靶点快照。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-01-01 Epub Date: 2024-01-19 DOI: 10.1080/14728222.2024.2306337

Mario Zoratti, Lucia Biasutto, Sofia Parrasia, Ildikó Szabo

引用次数: 0

TGF-β as a therapeutic target in the infarcted and failing heart: cellular mechanisms, challenges, and opportunities. TGF-β 作为梗塞和衰竭心脏的治疗靶点：细胞机制、挑战和机遇。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-01-01 Epub Date: 2024-02-19 DOI: 10.1080/14728222.2024.2316735

Nikolaos G Frangogiannis

{"title":"TGF-β as a therapeutic target in the infarcted and failing heart: cellular mechanisms, challenges, and opportunities.","authors":"Nikolaos G Frangogiannis","doi":"10.1080/14728222.2024.2316735","DOIUrl":"10.1080/14728222.2024.2316735","url":null,"abstract":"Introduction: Myocardial fibrosis accompanies most cardiac conditions and can be reparative or maladaptive. Transforming Growth Factor (TGF)-β is a potent fibrogenic mediator, involved in repair, remodeling, and fibrosis of the injured heart.Areas covered: This review manuscript discusses the role of TGF-β in heart failure focusing on cellular mechanisms and therapeutic implications. TGF-β is activated in infarcted, remodeling and failing hearts. In addition to its fibrogenic actions, TGF-β has a broad range of effects on cardiomyocytes, immune, and vascular cells that may have both protective and detrimental consequences. TGF-β-mediated effects on macrophages promote anti-inflammatory transition, whereas actions on fibroblasts mediate reparative scar formation and effects on pericytes are involved in maturation of infarct neovessels. On the other hand, TGF-β actions on cardiomyocytes promote adverse remodeling, and prolonged activation of TGF-β signaling in fibroblasts stimulates progression of fibrosis and heart failure.Expert opinion: Understanding of the cell-specific actions of TGF-β is necessary to design therapeutic strategies in patients with myocardial disease. Moreover, to implement therapeutic interventions in the heterogeneous population of heart failure patients, mechanism-driven classification of both HFrEF and HFpEF patients is needed. Heart failure patients with prolonged or overactive fibrogenic TGF-β responses may benefit from cautious TGF-β inhibition.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0