BJC reports最新文献

筛选

英文中文

Targeting the activated allosteric conformation of the endothelin receptor B in melanoma with an antibody-drug conjugate: mechanisms and therapeutic efficacy. 用抗体-药物偶联物靶向黑色素瘤中内皮素受体B的活化变构构象：机制和治疗效果。

BJC reports Pub Date : 2025-01-20 DOI: 10.1038/s44276-024-00109-y

Amaury Herbet, Marie Hautière, Frédéric Jean-Alphonse, Delphine Vivier, Christophe Leboeuf, Narciso Costa, Aloïse Mabondzo, Guilhem Bousquet, Franck Denat, Eric Reiter, Didier Boquet

{"title":"Targeting the activated allosteric conformation of the endothelin receptor B in melanoma with an antibody-drug conjugate: mechanisms and therapeutic efficacy.","authors":"Amaury Herbet, Marie Hautière, Frédéric Jean-Alphonse, Delphine Vivier, Christophe Leboeuf, Narciso Costa, Aloïse Mabondzo, Guilhem Bousquet, Franck Denat, Eric Reiter, Didier Boquet","doi":"10.1038/s44276-024-00109-y","DOIUrl":"10.1038/s44276-024-00109-y","url":null,"abstract":"Background: Endothelin 1 receptors are one of the drivers of tumor progression in many cancers. Inhibition of their signaling pathways with antagonist drugs has been the subject of numerous clinical trials, but the results have not met expectations probably due to the high endothelin concentrations in the tumor microenvironment and their unusually high affinity for their receptors.Methods: We previously reported the rendomab B49 antibody (RB49) exhibiting a preferential affinity for the activated conformation of human endothelin B receptor (ETB), not displaced by high endothelin levels, and without any pharmacological properties that could inhibit the division of melanoma cells. In this context, we have developed xiRB49-MMAE, a chimeric antibody-drug conjugated (ADC) to monomethyl auristatin E. We have characterized its physicochemical properties, studied its binding mechanisms, and evaluated its therapeutic potential in a preclinical model. Immunohistochemical analysis of metastatic melanoma lymph nodes evaluated RB49 as a diagnostic tool for patient stratification.Results: xiRB49-MMAE showed high efficacy against melanoma cells and ETB+ xenograft tumor models. IHC studies indicated that 100% of melanoma patient lymph node biopsies were RB49-positive.Conclusions: xiRB49-MMAE is a promising drug candidate for clinical trials in ETB+ tumors. RB49 could be used as a diagnostic tool for patient stratification.","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019878","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

A phase I study of the CDK4/6 inhibitor ribociclib combined with gemcitabine in patients with advanced solid tumors. CDK4/6抑制剂ribociclib联合吉西他滨治疗晚期实体瘤患者的I期研究

BJC reports Pub Date : 2025-01-14 DOI: 10.1038/s44276-024-00107-0

Aurora Norman, Mahesh Seetharam, Jacob Allred, Jianping Kong, Mateusz Opyrchal, Wen Wee Ma, Yanyan Lou, Grace K Dy, Amit Mahipal, S John Weroha, Andrea E Wahner Hendrickson, Joel M Reid, Alex A Adjei

{"title":"A phase I study of the CDK4/6 inhibitor ribociclib combined with gemcitabine in patients with advanced solid tumors.","authors":"Aurora Norman, Mahesh Seetharam, Jacob Allred, Jianping Kong, Mateusz Opyrchal, Wen Wee Ma, Yanyan Lou, Grace K Dy, Amit Mahipal, S John Weroha, Andrea E Wahner Hendrickson, Joel M Reid, Alex A Adjei","doi":"10.1038/s44276-024-00107-0","DOIUrl":"10.1038/s44276-024-00107-0","url":null,"abstract":"Background: Based on preclinical data showing addition of CDK4/6 inhibitors to gemcitabine was synergistic, ribociclib was evaluated in combination with gemcitabine to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT).Methods: In this single arm multicohort phase I trial, we evaluated the safety and efficacy of ribociclib plus gemcitabine in patients with advanced solid tumors. Patients received gemcitabine intravenously on days 1 and 8 followed by ribociclib days 8-14, with treatment repeated every 3 weeks.Results: The study enrolled 43 patients between October 2017 and September 2019. The escalation phase (19 patients) determined the MTD and recommended phase II dose (RP2D) to be ribociclib 800 mg daily and gemcitabine 1000 mg/m2 for the expansion phase (24 patients). One patient experienced Grade 4 thrombocytopenia. Eleven patients experienced Grade 3 adverse events (AE), the most common being neutropenia, thrombocytopenia, and anemia. No partial or complete responses were observed. 15/22 (68%) of efficacy evaluable patients who received the MTD achieved best response of stable disease.Conclusions: The addition of ribociclib to gemcitabine was tolerated well and yielded stability of tumors in both cohorts. Biomarkers such as Rb status and activity of CDK2 and CDK4/6 complexes may help to select patients who may respond better to the combination of gemcitabine and ribociclib.Clinical trial registration: NCT03237390.","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985971","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

Serum laminin γ2 monomer as a novel diagnostic and prognostic marker for pancreatic ductal adenocarcinoma. 血清层粘连蛋白γ - 2单体作为胰腺导管腺癌新的诊断和预后指标。

BJC reports Pub Date : 2025-01-14 DOI: 10.1038/s44276-024-00116-z

Takeshi Terashima, Kouki Nio, Naohiko Koshikawa, Makoto Ueno, Tadashi Toyama, Masaki Miyazawa, Tomoyuki Hayashi, Akihiro Seki, Hidetoshi Nakagawa, Noriho Iida, Shinya Yamada, Hajime Takatori, Tetsuro Shimakami, Toru Yoshimura, Eisaku Yoshida, Masatoshi Nakagawa, Motoharu Seiki, Taro Yamashita

{"title":"Serum laminin γ2 monomer as a novel diagnostic and prognostic marker for pancreatic ductal adenocarcinoma.","authors":"Takeshi Terashima, Kouki Nio, Naohiko Koshikawa, Makoto Ueno, Tadashi Toyama, Masaki Miyazawa, Tomoyuki Hayashi, Akihiro Seki, Hidetoshi Nakagawa, Noriho Iida, Shinya Yamada, Hajime Takatori, Tetsuro Shimakami, Toru Yoshimura, Eisaku Yoshida, Masatoshi Nakagawa, Motoharu Seiki, Taro Yamashita","doi":"10.1038/s44276-024-00116-z","DOIUrl":"10.1038/s44276-024-00116-z","url":null,"abstract":"Background: The identification of effective diagnostic and prognostic biomarkers is critical to improving the outcomes of patients with pancreatic ductal adenocarcinoma (PDAC). We explored the potential of serum levels of laminin γ2 monomer (LG2m) as a biomarker in PDAC.Methods: This study included two cohorts. Cohort 1 included 142 PDAC patients, 55 patients with intraductal papillary mucinous neoplasm (IPMN), and 46 healthy individuals. Cohort 2 included 518 PDAC patients. The medical records of patients were reviewed. Cut-off levels for LG2m were determined by receiver operating characteristic analysis.Results: In Cohort 1, serum LG2m levels were significantly higher in PDAC patients compared with healthy individuals (P < 0.001) and IPMN patients (P < 0.001). Comparing PDAC patients and health individuals, the optimal cut-off level of LG2m was 9.55 pg/mL and the sensitivity, specificity, and area under the curve were 0.89, 0.87, and 0.88, respectively. High sensitivity of LG2m in PDAC patients were confirmed in Cohort 2. The sensitivity and specificity of LG2m was higher than that of CEA and CA19-9. In patients treated with resection or chemotherapy, high serum LG2m level indicated a significantly shorter survival (P = 0.042 and P < 0.001, respectively).Conclusions: LG2m may be a useful diagnostic and prognostic marker for PDAC.","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985972","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

首页上一页