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Epiploic Appendagitis in a Breast Cancer Patient on Abemaciclib: Case Report. Abemaciclib治疗1例乳腺癌患者的网膜阑尾炎。
IF 1.7 4区 医学
Chemotherapy Pub Date : 2025-09-17 DOI: 10.1159/000548495
Juned Islam, Peta Hughes, Fiona Lam, Karen DeSouza
{"title":"Epiploic Appendagitis in a Breast Cancer Patient on Abemaciclib: Case Report.","authors":"Juned Islam, Peta Hughes, Fiona Lam, Karen DeSouza","doi":"10.1159/000548495","DOIUrl":"https://doi.org/10.1159/000548495","url":null,"abstract":"<p><strong>Introduction: </strong>Epiploic appendagitis is an uncommon cause of acute abdominal pain, often mimicking surgical emergencies. This case highlights the diagnostic process for epiploic appendagitis in a breast cancer patient receiving abemaciclib, a CDK4/6 (Cyclin-dependent Kinase) inhibitor, and discusses potential associations with targeted therapies.</p><p><strong>Case presentation: </strong>We present a case of a 48-year-old female on adjuvant abemaciclib for Stage IIIA breast cancer who developed acute left iliac fossa (LIF) pain. Clinical assessment, laboratory investigations, transvaginal ultrasound, and subsequent computed tomography (CT) imaging of the abdomen and pelvis were performed to establish the diagnosis. CT imaging revealed a characteristic oval fat-density lesion with surrounding inflammation adjacent to the sigmoid colon, consistent with epiploic appendagitis. Other differential diagnoses, including ovarian pathology and diverticulitis, were excluded. The patient was managed conservatively with analgesia, and the abemaciclib was temporarily discontinued and restarted at a lower dose, leading to symptom resolution. This case underscores the importance of considering epiploic appendagitis in the differential diagnosis of acute abdominal pain, particularly in patients on targeted therapies like abemaciclib, which are known to have gastrointestinal side effects. Timely and accurate diagnosis via imaging avoided unnecessary surgical intervention.</p><p><strong>Conclusion: </strong>This case is the first of its kind to propose a novel association between the use of targeted therapies such as abemaciclib and the development of inflammatory conditions such as epiploic appendagitis. It emphasises the crucial role of clinical suspicion and appropriate imaging in establishing this rare diagnosis. Further research is warranted to explore potential links between CDK4/6 inhibitors and the development of epiploic appendagitis.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"1-15"},"PeriodicalIF":1.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Therapeutic Drug Monitoring: A Driver to Precision Medicine for Patients with Hematological Malignancies. 治疗药物监测——血液系统恶性肿瘤患者精准用药的驱动因素。
IF 1.7 4区 医学
Chemotherapy Pub Date : 2025-08-11 DOI: 10.1159/000547073
Jannik Stemler, Roger M Brüggemann, Nick A de Jonge
{"title":"Therapeutic Drug Monitoring: A Driver to Precision Medicine for Patients with Hematological Malignancies.","authors":"Jannik Stemler, Roger M Brüggemann, Nick A de Jonge","doi":"10.1159/000547073","DOIUrl":"10.1159/000547073","url":null,"abstract":"<p><strong>Background: </strong>Targeted therapies have revolutionized the treatment of hematological malignancies, offering improved efficacy with fewer off-target effects compared to traditional chemotherapy. However, significant pharmacokinetic (PK) and pharmacodynamic (PD) variability exists among patients receiving these therapies.</p><p><strong>Summary: </strong>Therapeutic drug monitoring (TDM) measures drug exposure and thereby helps to adjust the dose of a drug to maintain its concentration within a target range. It is frequently applied for drugs with characteristics like PK variability or narrow therapeutic window, among others, to ensure optimal therapeutic outcome while minimizing adverse effects. Many molecular targeted agents (MTAs) for malignancies, especially tyrosine kinase inhibitors, exhibit significant variability in exposure, and yet are still dosed with a \"one-size-fits-all\" approach. While this is partially culprit to regulatory approval requirements of MTA, it contradicts principles of targeted therapy. PK/PD variability necessitates a personalized approach to dosing in order to optimize therapeutic outcomes and minimize toxicity. TDM provides an avenue to refine dosing strategies based on individual patient characteristics.</p><p><strong>Key messages: </strong>Through incorporation of TDM, treatment of hematological malignancies could move toward target concentration-driven dosing in clinical trials and regulatory frameworks. Establishing target concentrations for MTA requires solid exposure-response and exposure-toxicity analyses in the population of interest. To establish such reference ranges, large populational analyses are necessitated, underlining the importance of the incorporation of such endpoints into phase III trials. Economic restrictions, sample transportation logistics, turnaround times, and interpretation may hinder the application of a TDM-guided dosing approach in routine care. Ultimately, personalized TDM-guided dosing could improve patient outcomes and quality of life through minimizing toxicity.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"1-7"},"PeriodicalIF":1.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 a Therapeutic Drug Monitoring-Guided Strategy of Isavuconazole for Optimizing Efficacy/Safety Outcomes in Onco-Hematological Pediatric Patients: A Systematic Review. tdm引导的异戊康唑策略在优化儿童肿瘤血液病患者的疗效/安全性结局中的作用:一项系统综述
IF 1.7 4区 医学
Chemotherapy Pub Date : 2025-08-05 DOI: 10.1159/000547799
Milo Gatti, Pier Giorgio Cojutti, Federico Pea
{"title":"Role of a Therapeutic Drug Monitoring-Guided Strategy of Isavuconazole for Optimizing Efficacy/Safety Outcomes in Onco-Hematological Pediatric Patients: A Systematic Review.","authors":"Milo Gatti, Pier Giorgio Cojutti, Federico Pea","doi":"10.1159/000547799","DOIUrl":"10.1159/000547799","url":null,"abstract":"<p><strong>Introduction: </strong>Evidence concerning the implementation of a therapeutic drug monitoring (TDM)-guided approach for optimizing isavuconazole exposure in onco-hematological pediatric patients is limited. The aim of this systematic review was to summarize the current evidence about the role that a TDM-guided strategy of isavuconazole may have in optimizing efficacy/safety outcomes of invasive fungal infection (IFI) treatment/prophylaxis among onco-hematological pediatric patients.</p><p><strong>Methods: </strong>Two authors independently searched the PubMed-MEDLINE and Scopus databases up to 25 April 2025, to retrieve randomized controlled trials or observational studies providing real-life data assessing isavuconazole exposure according to a TDM-guided approach in pediatric patients, and evaluating the relationship between isavuconazole exposure and efficacy/safety outcomes. Data were independently extracted by the two authors, and the quality of the included studies was independently assessed by means of the Cochrane Risk of Bias Tool (RoB 2.0) in case of randomized controlled trials, and by means of the Newcastle-Ottawa scale in case of observational studies and case series. Mortality attributable to IFI and hepatotoxicity occurrence were selected as primary outcomes. Descriptive statistics were used for summarizing the retrieved data.</p><p><strong>Results: </strong>After screening 577 articles, eight studies were included in the systematic review (five retrospective observational cohort studies and 3 case series; n = 116). Attainment of optimal isavuconazole exposure at first TDM assessment ranged from 36.7% to 83.3% of included patients, being underexposure reported in up to 40.0% of cases. Overall, mortality attributable to IFI occurred in 10 out of 59 patients (16.9%) in which this outcome was evaluated, being associated with isavuconazole underexposure only in 30.0% of cases. Hepatotoxicity occurred in 14 out of 78 included patients (17.9%), being related to isavuconazole overexposure in 50.0% of cases.</p><p><strong>Conclusion: </strong>Despite limited findings, our systematic review may support a potential role for a TDM-guided strategy in optimizing isavuconazole exposure among onco-hematological pediatric patients, particularly considering both the non-negligible proportion of cases who failed in attaining optimal exposure with standard dosing regimens.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"1-14"},"PeriodicalIF":1.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Endoplasmic Reticulum Stress Modulates Therapeutic Responses in Hepatocellular Carcinoma. 内质网应激调节肝癌的治疗反应。
IF 1.7 4区 医学
Chemotherapy Pub Date : 2025-08-04 DOI: 10.1159/000545341
Yi-Li Chen, Chen-Wei Chou, I-Hsiu Liu, Yuh-Harn Wu, Cheng-Yi Chen
{"title":"Endoplasmic Reticulum Stress Modulates Therapeutic Responses in Hepatocellular Carcinoma.","authors":"Yi-Li Chen, Chen-Wei Chou, I-Hsiu Liu, Yuh-Harn Wu, Cheng-Yi Chen","doi":"10.1159/000545341","DOIUrl":"10.1159/000545341","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is one of the primary types of liver cancer, and the mortality trend of HCC patients is estimated to continue rising in the future. Chemotherapy drugs or targeted therapies are considered primary treatment modalities for intermediate-stage or advanced-stage HCC. Although these drugs can extend the survival rate of HCC patients, prolonged treatment often raises concerns about drug resistance or cancer recurrence, leading to undesirable therapeutic outcomes. Drug treatments generally involve promoting cytotoxicity and inhibiting oncogenic signaling pathways, and the response of cancer cells to drug-induced stress situations may potentially impact the effectiveness of treatment. The unfolded protein response (UPR) acts as a cellular stress response mechanism, activating pathways such as DNA repair and autophagy to help cellular survival when cells are damaged. It has also been shown that under sustained or excessive stress, UPR can control cell fate toward programmed cell death, such as apoptosis. Previous studies have found that activation of UPR plays an essential role in cancer cell growth and drug resistance. Various molecules or signaling pathways regulated by the UPR assist cancer cells in responding to anticancer drugs, enabling their survival during treatment.</p><p><strong>Summary: </strong>The present review illustrated genetic molecules or signaling pathways controlled by the UPR and investigates their influence on liver cancer drugs. Moreover, the review also summarizes the partial effects of UPR, including lipid droplet formation and inflammatory stimulation, and their roles in HCC development and drug resistance, respectively.</p><p><strong>Key message: </strong>Unraveling and targeting ER stress provide potential therapeutic strategies for HCC treatment.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"1-16"},"PeriodicalIF":1.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Gaza's First Polio Case in 25 Years: Is Health Infrastructure Collapse Threatening Resilience? 加沙 25 年来首次出现脊髓灰质炎病例:卫生基础设施的崩溃是否威胁到复原力?
IF 2 4区 医学
Chemotherapy Pub Date : 2025-01-01 Epub Date: 2024-10-14 DOI: 10.1159/000541933
Francesco Branda, Giancarlo Ceccarelli, Marta Giovanetti, Massimo Ciccozzi, Fabio Scarpa
{"title":"Gaza's First Polio Case in 25 Years: Is Health Infrastructure Collapse Threatening Resilience?","authors":"Francesco Branda, Giancarlo Ceccarelli, Marta Giovanetti, Massimo Ciccozzi, Fabio Scarpa","doi":"10.1159/000541933","DOIUrl":"10.1159/000541933","url":null,"abstract":"","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"9-11"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Importance of Sex-Dependent Differences for Dosing Selection and Optimization of Chemotherapeutic Drugs. 性别差异对化疗药物剂量选择和优化的重要性。
IF 2 4区 医学
Chemotherapy Pub Date : 2025-01-01 Epub Date: 2024-11-07 DOI: 10.1159/000542461
Claire Seydoux, Myriam Briki, Anna D Wagner, Eva Choong, Monia Guidi, Sandro Carrara, Yann Thoma, Françoise Livio, François R Girardin, Catia Marzolini, Thierry Buclin, Laurent A Decosterd
{"title":"Importance of Sex-Dependent Differences for Dosing Selection and Optimization of Chemotherapeutic Drugs.","authors":"Claire Seydoux, Myriam Briki, Anna D Wagner, Eva Choong, Monia Guidi, Sandro Carrara, Yann Thoma, Françoise Livio, François R Girardin, Catia Marzolini, Thierry Buclin, Laurent A Decosterd","doi":"10.1159/000542461","DOIUrl":"10.1159/000542461","url":null,"abstract":"<p><strong>Background: </strong>Despite major advances in cancer treatment in the past years, there is a need to optimize chemotherapeutic drug dosing strategies to reduce toxicities, suboptimal responses, and the risk of relapse. Most cancer drugs have a narrow therapeutic index with substantial pharmacokinetics variability. Yet, current dosing approaches do not fully account for the complex pathophysiological characteristics of the patients. In this regard, the effect of sex on anticancer chemotherapeutic drugs' disposition is still underexplored. In this article, we review sex differences in chemotherapeutic drug pharmacokinetics; we suggest a novel approach that integrates sex into the traditional a priori body surface area (BSA) dosing selection model, and finally, we provide an overview of the potential benefits of a broader use of therapeutic drug monitoring (TDM) in oncology.</p><p><strong>Summary: </strong>To date, anticancer chemotherapeutic drug dosing is most often determined by BSA, a method widely used for its ease of practice, despite criticism for not accounting for individual factors, notably sex. Anatomical, physiological, and biological differences between males and females can affect pharmacokinetics, including drug metabolism and clearance. At equivalent doses, females tend to display higher circulating exposure and more organ toxicities, which has been formally demonstrated at present for about 20% of chemotherapeutic drugs. An alternative could be the sex-adjusted BSA (SABSA), incorporating a 10% increase in dosing for males and a 10% decrease for females, though this approach still lacks formal clinical validation. Another strategy to reduce treatment-related toxicity and potentially enhance clinical outcomes could be a more widespread use of TDM, for which a benefit has been demonstrated for 5-fluorouracil, busulfan, methotrexate, or thiopurines.</p><p><strong>Key messages: </strong>The inclusion of sex besides BSA in an easy-to-implement formula such as SABSA could improve a priori chemotherapy dosing selection, even though it still requires clinical validation. The a posteriori use of TDM could further enhance treatment efficacy and safety in oncology.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"92-101"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Phase I Clinical Study of a Multi-Kinase Inhibitor TG02 Capsule for the Treatment of Recurrent High-Grade Gliomas with Failed Temozolomide Treatment in Chinese Patients. 多激酶抑制剂 TG02 胶囊治疗替莫唑胺治疗失败的中国复发性高级别胶质瘤的 I 期临床研究。
IF 2 4区 医学
Chemotherapy Pub Date : 2025-01-01 Epub Date: 2024-11-18 DOI: 10.1159/000542365
Cheng-Cheng Guo, Qun-Ying Yang, Shao-Yan Xi, Jian Zhou, Zhi-Huan Zhou, Xi Cao, Yi-Xiang Liao, Benjamin Xiao-Yi Li, Xiang-Rong Dai, Michael Wong, Yu-Jie Li, Xiao-Hui Yu, Zhong-Ping Chen
{"title":"Phase I Clinical Study of a Multi-Kinase Inhibitor TG02 Capsule for the Treatment of Recurrent High-Grade Gliomas with Failed Temozolomide Treatment in Chinese Patients.","authors":"Cheng-Cheng Guo, Qun-Ying Yang, Shao-Yan Xi, Jian Zhou, Zhi-Huan Zhou, Xi Cao, Yi-Xiang Liao, Benjamin Xiao-Yi Li, Xiang-Rong Dai, Michael Wong, Yu-Jie Li, Xiao-Hui Yu, Zhong-Ping Chen","doi":"10.1159/000542365","DOIUrl":"10.1159/000542365","url":null,"abstract":"<p><strong>Introduction: </strong>We report the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of a multi-kinase inhibitor (TG02 capsule) as a new therapy for patients with recurrent high-grade gliomas in China.</p><p><strong>Methods: </strong>This is a single-center, dose-escalation, open-label phase I study, which enrolled patients with recurrent high-grade gliomas who failed to temozolomide. Patients were assigned sequentially into different dose groups and received TG02 every 4 weeks. The dose was increased in a traditional 3 + 3 design. Primary endpoints were the dose-limited toxicity (DLT) and the maximum tolerated dose (MTD).</p><p><strong>Results: </strong>Twelve patients (8 glioblastomas, 4 diffuse astrocytoma) were enrolled between May 2019 and November 2021. Three patients received 100 mg and 9 received 150 mg TG02 twice a week. The plasma concentration of TG02 reached the maximum at 2 h after administration, and the elimination half-life was about 7 h. No DLT occurred and MTD was not defined in this study. Eleven patients had one or more investigator-assessed treatment-related adverse events (TRAEs). The most frequent TRAEs were vomiting (91.7%) and diarrhea (75.0%), and 50% of the patients had grade 3 or 4 adverse events. There were no treatment-related deaths. The median progression-free survival and overall survival were 1.77 (95% confidence interval [CI]: 0.82-4.24) and 9.63 (95% CI: 2.66-not estimated) months, respectively.</p><p><strong>Conclusions: </strong>TG02 capsule 150 mg twice a week is safe and tolerable in Chinese patients with recurrent high-grade gliomas. Patients who failed to temozolomide showed obvious tumor reduction when switching to TG02 capsule. The efficacy of recurrent gliomas warrants further investigation.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"74-84"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Downregulation of Rad51 Expression and Activity Potentiates the Cytotoxic Effect of Osimertinib in Human Non-Small Cell Lung Cancer Cells. 下调 Rad51 的表达和活性可增强奥希替尼对人类非小细胞肺癌细胞的细胞毒性作用。
IF 2 4区 医学
Chemotherapy Pub Date : 2025-01-01 Epub Date: 2024-08-10 DOI: 10.1159/000540867
Jen-Chung Ko, Jyh-Cheng Chen, Ching-Hsiu Huang, Pei-Jung Chen, Qiao-Zhen Chang, Bo-Cheng Mu, Jun-Jie Chen, Tzu-Yuan Tai, Kasumi Suzuki, Yi-Xuan Wang, Yun-Wei Lin
{"title":"Downregulation of Rad51 Expression and Activity Potentiates the Cytotoxic Effect of Osimertinib in Human Non-Small Cell Lung Cancer Cells.","authors":"Jen-Chung Ko, Jyh-Cheng Chen, Ching-Hsiu Huang, Pei-Jung Chen, Qiao-Zhen Chang, Bo-Cheng Mu, Jun-Jie Chen, Tzu-Yuan Tai, Kasumi Suzuki, Yi-Xuan Wang, Yun-Wei Lin","doi":"10.1159/000540867","DOIUrl":"10.1159/000540867","url":null,"abstract":"<p><strong>Introduction: </strong>Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has shown significant clinical benefits in patients with EGFR-sensitizing mutations or the EGFR T790M mutation. The homologous recombination (HR) pathway is crucial for repairing DNA double-strand breaks (DSBs). Rad51 plays a central role in HR, facilitating the search for homology and promoting DNA strand exchange between homologous DNA molecules. Rad51 is overexpressed in numerous types of cancer cells. B02, a specific small molecule inhibitor of Rad51, inhibits the DNA strand exchange activity of Rad51. Previous studies have indicated that B02 disrupted Rad51 foci formation in response to DNA damage and inhibited DSBs repair in human cells and sensitized them to chemotherapeutic drugs in vitro and in vivo. However, the potential therapeutic effects of combining osimertinib with a Rad51 inhibitor are not well understood. The aim of this study was to elucidate whether the downregulation of Rad51 expression and activity can enhance the osimertinib-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells.</p><p><strong>Methods: </strong>We used the MTS, trypan blue dye exclusion and colony-formation ability assay to determine whether osimertinib alone or in combination with B02 had cytotoxic effects on NSCLC cell lines. Real-time polymerase chain reaction was conducted to measure the amounts of Rad51 mRNA. The protein levels of phosphorylated AKT and Rad51 were determined by Western blot analysis.</p><p><strong>Results: </strong>We found that osimertinib reduced Rad51 expression by inactivating AKT activity. Rad51 knockdown using small interfering RNA or AKT inactivation through the phosphatidylinositol 3-kinase inhibitor LY294002 or si-AKT RNA transfection enhanced the cytotoxic and growth inhibitory effects of osimertinib. In contrast, AKT-CA (a constitutively active form of AKT) vector-enforced expression could mitigate the cytotoxic and cell growth inhibitory effects of osimertinib. Furthermore, B02 significantly enhanced the cytotoxic and cell growth inhibitory effects of osimertinib in NSCLC cells. Compared to parental cells, the activation of AKT and Rad51 expression in osimertinib-resistant cells could not be significantly inhibited by osimertinib treatment. Moreover, the increased expression of Rad51 is associated with the resistance mechanism in osimertinib-resistant H1975 and A549 cells.</p><p><strong>Conclusion: </strong>Collectively, the downregulation of Rad51 expression and activity enhances the cytotoxic effect of osimertinib in human NSCLC cells.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"12-25"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Therapeutic Drug Monitoring of Imatinib: Is There a Rationale for Also Quantifying Its Active Metabolite? 伊马替尼的治疗药物监测:同时量化其活性代谢物是否合理?
IF 2 4区 医学
Chemotherapy Pub Date : 2025-01-01 Epub Date: 2024-10-11 DOI: 10.1159/000541936
Clara Eschalier, Thierry Lafont, Sabrina Marsili, Malika Yakoubi, Aurélie Brice, Fabienne Thomas, Mélanie White-Koning, Ben Allal, Etienne Chatelut
{"title":"Therapeutic Drug Monitoring of Imatinib: Is There a Rationale for Also Quantifying Its Active Metabolite?","authors":"Clara Eschalier, Thierry Lafont, Sabrina Marsili, Malika Yakoubi, Aurélie Brice, Fabienne Thomas, Mélanie White-Koning, Ben Allal, Etienne Chatelut","doi":"10.1159/000541936","DOIUrl":"10.1159/000541936","url":null,"abstract":"<p><strong>Introduction: </strong>Therapeutic drug monitoring of imatinib is widely performed to individualize imatinib dosage. While N-desmethyl imatinib is an active metabolite of imatinib, its concentrations are not routinely determined.</p><p><strong>Methods: </strong>Imatinib and N-desmethyl imatinib trough plasma concentrations at steady-state were obtained from 295 patients with either chronic myeloid leukemia or gastrointestinal stromal tumor to see whether N-desmethyl imatinib provided additional information. Pharmacokinetic data were analyzed using a nonlinear mixed effect approach. Correlations between several pharmacokinetic metrics of drug exposure were evaluated.</p><p><strong>Results: </strong>The mean value of the N-desmethyl imatinib/imatinib ratio of trough concentrations was 0.31 with half of the values between 0.23 and 0.37. N-desmethyl imatinib and total (i.e., N-desmethyl imatinib plus imatinib) trough plasma concentrations or area under the curve values were closely correlated with imatinib values. The distribution of imatinib or total concentrations between patients requiring imatinib dosage adjustment, or not, was similar.</p><p><strong>Conclusion: </strong>These results do not clearly support routine N-desmethyl monitoring since it does not provide additional information to imatinib data.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"26-36"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Primary Squamous Cell Carcinoma of the Duodenum: A Case Report and Literature Review. 十二指肠原发性鳞状细胞癌:病例报告和文献综述。
IF 2 4区 医学
Chemotherapy Pub Date : 2025-01-01 Epub Date: 2024-11-11 DOI: 10.1159/000542485
Yifan Hui, Fei Ke, Wei Lu, Wenli Qiu, Xia Zheng, Haibo Cheng
{"title":"Primary Squamous Cell Carcinoma of the Duodenum: A Case Report and Literature Review.","authors":"Yifan Hui, Fei Ke, Wei Lu, Wenli Qiu, Xia Zheng, Haibo Cheng","doi":"10.1159/000542485","DOIUrl":"10.1159/000542485","url":null,"abstract":"<p><strong>Introduction: </strong>Duodenal squamous cell carcinoma is an exceedingly rare occurrence among gastrointestinal malignancies, and its diagnosis and treatment are not well understood.</p><p><strong>Case presentation: </strong>In this report, we present a case of duodenal squamous cell carcinoma with liver and adrenal metastasis. The patient was treated with gemcitabine and S-1, achieving a progression-free survival of 7 months and an overall survival of 9 months. Additionally, we review the features and treatment approaches reported in previous cases of primary duodenal carcinoma.</p><p><strong>Conclusion: </strong>Clearly, further case reports, such as ours, can contribute to a deeper understanding that is essential for characterizing this entity and establishing management guidelines.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"102-108"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
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