Cts-Clinical and Translational Science最新文献

{"title":"The Edges of Clinical Pharmacology: A Narrative Review on Religious and Sociocultural Influences in Drug Management","authors":"Salvatore Di Maria,&nbsp;Alessio Provenzani","doi":"10.1111/cts.70217","DOIUrl":"https://doi.org/10.1111/cts.70217","url":null,"abstract":"<p>Scientific advancements in pharmacology have revolutionized disease management, significantly enhancing global health. Innovations like biological therapies and mRNA vaccines underscore the field's capacity to address complex conditions and global crises. However, significant challenges remain, including individual biological variations and ethical, cultural, and religious barriers, which complicate treatment access and equity. This review explores these global barriers, emphasizing the intersection of pharmacology with diverse cultural contexts. Religious beliefs often shape attitudes toward treatments. For example, fasting during Ramadan requires careful adjustments to diabetes management protocols, while Jehovah's Witnesses' refusal of blood transfusions necessitates alternative solutions like hemoglobin-based oxygen carriers and cell-saving devices. In Africa, cultural resistance to blood sampling impacts disease diagnosis and therapeutic drug monitoring, highlighting the need for culturally sensitive healthcare strategies. Dietary restrictions rooted in religious practices, such as Kashrut and Halal, further complicate drug formulation. Medications containing animal-derived ingredients may be rejected, necessitating plant-based or certified alternatives. Emergency exceptions in Islamic and Jewish law provide some flexibility, but overall, these challenges underscore the necessity of innovative solutions to ensure inclusive healthcare. This narrative review advocates for an equitable approach to pharmacological research and clinical practice, emphasizing the importance of dialogue and cultural awareness. By addressing ethical dilemmas and respecting diverse traditions, pharmacology can better serve global populations, bridging gaps between modern medicine and cultural values. The review calls for tailored strategies that uphold both medical efficacy and cultural sensitivity to advance healthcare equity worldwide.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70217","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741187","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":"Effect of Cladribine Tablets on the Pharmacokinetics of a Combined Oral Contraceptive in Pre-Menopausal Women With Relapsing Multiple Sclerosis","authors":"Robert Hermann,&nbsp;Kerstin Hellwig,&nbsp;Sumedh Gaikwad,&nbsp;Andrew Galazka,&nbsp;Afrim Bytyqi,&nbsp;Dominic Jack,&nbsp;Axel Krebs-Brown,&nbsp;Claudia Vetter,&nbsp;Axel Nolting,&nbsp;Karthik Venkatakrishnan,&nbsp;Jennifer Q. Dong","doi":"10.1111/cts.70204","DOIUrl":"https://doi.org/10.1111/cts.70204","url":null,"abstract":"<p>This study assessed the effect of cladribine tablets (CladT) on the pharmacokinetics (PK) of a combined oral contraceptive (COC) in pre-menopausal women with relapsing multiple sclerosis. It was a randomized, double-blind, two-period, two-sequence crossover study to assess steady-state plasma PK (area under the concentration–time curve and peak concentration) of COC (ethinylestradiol [EE] 30 μg and levonorgestrel [LNG] 150 μg) when co-administered with CladT or placebo. Participants received 2 weeks of active CladT treatment per course (Weeks 1 and 5 per year) to have a cumulative dose of 3.5 mg/kg over 2 years as per label. Of the 24 randomized participants, 23 completed the study. The results showed that the concentration–time profiles as well as PK parameters of EE and LNG in the plasma were similar when co-administered with CladT or placebo. Analysis of variance confirmed the bioequivalence of EE and LNG in COC when co-administered with either CladT or placebo. All participants were adequately exposed to cladribine. Repeat-dose administration of CladT had no apparent effect on serum luteinizing hormone, follicle-stimulating hormone, progesterone, or sex hormone-binding globulin concentrations during concomitant treatment with COC. Co-administration with COC did not change the known safety and tolerability profile of CladT and did not alter the PK of EE or LNG in a COC during the study. Therefore, the concomitant use of CladT is not expected to decrease the efficacy of COCs containing EE and LNG.</p><p><b>Trial Registration:</b> EudraCT Number: 2018-001015-70.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749418","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":"A First-In-Human Phase 1 Study to Evaluate the Safety and Tolerability of LEM-S401, a Novel siRNA-DegradaBALL Drug Targeting CTGF in Healthy Adults","authors":"Ha-Yeon Kim,&nbsp;Jaeso Cho,&nbsp;Min Kyu Park,&nbsp;Dal-Hee Min,&nbsp;Jun Gi Hwang,&nbsp;Cheolhee Won","doi":"10.1111/cts.70207","DOIUrl":"https://doi.org/10.1111/cts.70207","url":null,"abstract":"<p>This study evaluated the safety, tolerability, and pharmacokinetics of LEM-S401, a novel siRNA therapeutic with DegradaBALL, a mesoporous silica nanoparticle-based delivery system. LEM-S401 is designed to deliver siRNA targeting connective tissue growth factor (CTGF) to fibroblasts for treating hypertrophic scars and keloids, both of which result from abnormal collagen proliferation. LEM-S401, containing unmodified siRNA LEM-17234 encapsulated in DegradaBALL nanoparticles, was administered subcutaneously to healthy adults in a randomized, double-blind, placebo-controlled, single-ascending dose study. Safety and tolerability assessments included vital signs, adverse events (AEs), laboratory tests, and cytokine levels. Pharmacokinetic analysis of LEM-17234 and silicon (Si), the primary component of DegradaBALL, was performed using blood samples collected at specified time points. LEM-S401 demonstrated a favorable safety and tolerability profile with only mild, self-resolving injection site reactions including pain and erythema. No systemic AEs were observed, and cytokine levels showed no significant changes between the treatment and placebo groups. Pharmacokinetic analysis revealed that LEM-17234 was below the plasma detection limit, indicating no notable systemic exposure of siRNA, while Si showed no dose-dependent systemic exposure, suggesting minimal systemic circulation of the mesoporous silica nanoparticles. These findings suggest DegradaBALL effectively encapsulates and delivers siRNA locally without significant systemic exposure. The novel DegradaBALL delivery system enables the stable and targeted delivery of siRNA, which presumably overcomes challenges related to siRNA instability and off-target effects. LEM-S401 has the potential to advance the treatment of fibrotic skin diseases such as keloids and hypertrophic scars by delivering siRNA directly to fibroblasts, thereby inhibiting excessive collagen production.</p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT04707131. https://clinicaltrials.gov/study/NCT04707131?cond=NCT04707131&amp;rank=1</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741636","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":"CYP3A Genotype Is Associated With Variability in the Exposure and Clearance of the Novel Oncogenic Transcription Inhibitor Lurbinectedin","authors":"Rubin Lubomirov,&nbsp;Laura Pérez-Ramos,&nbsp;Salvador Fudio,&nbsp;Eduardo Asín-Prieto,&nbsp;Laura Ibarra-Gómez,&nbsp;Pablo Zubiaur","doi":"10.1111/cts.70173","DOIUrl":"https://doi.org/10.1111/cts.70173","url":null,"abstract":"<p>Lurbinectedin is an oncogenic transcription inhibitor indicated for the treatment of small cell lung cancer (SCLC), which has also shown activity against other malignancies. In this work, two independent cohorts of 180 (discovery cohort) and 719 (validation cohort) cancer patients receiving lurbinectedin in Phases I, II, or III clinical trials were enrolled. Using a population pharmacokinetic (popPK) model of the discovery cohort, patients with extremely high (<i>n</i> = 10, cohort 1) and low (<i>n</i> = 10, cohort 2) etaCL values (i.e., a variable used as a surrogate of unexplained CL interindividual variability) were identified. They were sequenced for 42 candidate genes involved in lurbinectedin pharmacokinetics. A total of 34 variants located in 20 genes were significantly associated with lurbinectedin etaCL; the best nine hits (located in <i>CYP3A5, CYP3A4, ABCB1, ARNT, NR5A2, NR1H4</i>, and <i>FOXA3</i>) were subsequently genotyped in the validation cohort. A strong additive association between <i>CYP3A4</i> and <i>CYP3A5</i> genotypes (informed as a CYP3A activity score [AS] variable) and lurbinectedin clearance (CL) and exposure was confirmed, for example, patients with an AS of 3, 2, or 1 showed a 2.3-, 1.6-, and 1.5-fold higher total lurbinectedin CL compared to those with an AS of 0 and 2.3-, 1.8-, and 1.6-fold higher unbound lurbinectedin CL. In conclusion, preemptive <i>CYP3A</i> genotyping may offer a valuable approach for personalizing treatment with lurbinectedin in cancer patients.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70173","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717395","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":"Robust UPLC–MS/MS Method With Acetonitrile for Precise Intracellular Quantification of Tacrolimus in PBMCs: A Step Toward Clinical Integration","authors":"Napatsanan Tanathitiphuwarat,&nbsp;Asada Leelahavanichkul,&nbsp;Pajaree Chariyavilaskul,&nbsp;Suwasin Udomkarnjananun","doi":"10.1111/cts.70210","DOIUrl":"https://doi.org/10.1111/cts.70210","url":null,"abstract":"<p>Monitoring whole blood tacrolimus concentrations is standard in clinical practice; however, it may not fully reflect its therapeutic effects, as tacrolimus primarily acts within lymphocytes. While various intracellular quantification methods have been developed, many involve complex procedures such as evaporation, reconstitution, or specialized tools (e.g., magnetic beads, online solid-phase extraction), limiting their accessibility. This study aimed to develop and validate a streamlined, sensitive method for measuring intracellular tacrolimus concentrations using 5×10⁵ peripheral blood mononuclear cells (PBMCs). Tacrolimus concentrations were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). PBMCs were aliquoted into 50 μL volumes containing 5×10⁵ cells and prepared via acetonitrile-based protein precipitation. Chromatographic separation was performed using a Luna C18 column with a gradient mobile phase consisting of water with 20 mM ammonium acetate, 0.1% formic acid, and methanol at a flow rate of 0.4 mL/min. The method demonstrated excellent linearity between 0.1 and 25 ng/mL, corresponding to intracellular concentrations of 1–250 pg/5×10⁵ cells (<i>r</i>² = 0.999). Intra- and interday accuracy ranged from 98.1% to 109.8%, with precision between 2.08% and 8.70% across validation runs. Extraction recovery was high (93.0%–97.2%), with minimal matrix effects (100.9% at low QC and 111.6% at high QC). This validated LC-MS/MS method provides a rapid, reliable, and sensitive approach for pharmacokinetic studies and clinical applications, facilitating intracellular tacrolimus monitoring in transplant patients.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707643","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":"A Patient Centric Model for Vaso-Occlusive Crises in Sickle Cell Disease—Outcomes of a Consensus Exercise Conducted Across Patients and Experts","authors":"Pooja Nandi,&nbsp;Robert Ellis,&nbsp;Ankita Deshpande","doi":"10.1111/cts.70197","DOIUrl":"https://doi.org/10.1111/cts.70197","url":null,"abstract":"<p>Sickle cell disease (SCD) is a group of inherited disorders caused by a mutation in the beta globin gene that leads to sickling of red blood cells and results in anemia and Vaso-occlusive crises (VOC). VOC are described as an acute worsening of symptoms impacting daily life and often requiring treatment to resolve. A majority of SCD interventional trial endpoints consider VOC that require attendance at a health facility and do not account for VOC managed at home. These studies report lower VOC incidence compared to those that consider VOC managed both in the healthcare setting and at home. This presents challenges to the consistent and accurate assessment of treatment effect in reducing overall VOC count. This paper outlines a USA consensus exercise conducted with patients and a scientific expert review committee to develop a patient-centric VOC model that may apply across incidences, individuals, and treatment settings. The model is supported by a monitoring biomarker specification for the objective identification and classification of VOC taking place in the healthcare setting and at home. We additionally propose hardware, software, diaries, and patient-reported outcomes for an initial instrument design to evaluate the potential of the model in a validation study.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70197","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698808","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":"MoLPre: A Machine Learning Model to Predict Metastasis of cT1 Solid Lung Cancer","authors":"Jie Lan,&nbsp;Heng Wang,&nbsp;Jing Huang,&nbsp;Weiyi Li,&nbsp;Min Ao,&nbsp;Wanfeng Zhang,&nbsp;Junhao Mu,&nbsp;Li Yang,&nbsp;Longke Ran","doi":"10.1111/cts.70186","DOIUrl":"https://doi.org/10.1111/cts.70186","url":null,"abstract":"<p>Given that more than 20% of patients with cT1 solid NSCLC showed nodal or extrathoracic metastasis, early detection of metastasis is crucial and urgent for improving therapeutic planning and patients' risk stratification in clinical practice. This study collected clinicopathological variables from the pulmonary nodule and lung cancer database of the First Affiliated Hospital of Chongqing Medical University, where patients with early-stage (cT1) solitary lung cancer were evaluated from 2018.11 to 2022.10. The random forest model and Shapley Additive Explanations (SHAP) were used to investigate the importance of clinical features in the feature selection part. Random Forest, Gradient Boosting, and AdaBoost classifiers were applied to build the final model, and the predictive discrimination of each model was compared based on the receiver operating characteristics (ROC) curve and precision and recall curve. With the evaluation of feature importance, 9 features were used to construct the prediction model finally. The Random Forest model yielded an average precision of 0.93 with an area under the curve (AUC) of 0.92 (95% CI: 0.88–0.94) compared with the Gradient Boosting and AdaBoost classifiers in the internal validation dataset, yielding an average precision of 0.87 and 0.91 with AUCs of 0.87 (95% CI: 0.84–0.93) and 0.90 (95% CI: 0.86–0.92), respectively. In addition, the Random Forest classifier performed best in 5 other 5 diagnostic indices. Furthermore, we embedded this model in a web application called MoLPre (https://molpre.cqmu.edu.cn/), a user-friendly tool assisting in the metastasis prediction of cT1 solid lung cancer.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707210","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":"Comparison of Molnupiravir Exposure-Response Relationships for Virology Response and Mechanism of Action Biomarkers With Clinical Outcomes in Treatment of COVID-19","authors":"Akshita Chawla,&nbsp;Ruthie Birger,&nbsp;Brian M. Maas,&nbsp;Youfang Cao,&nbsp;Hong Wan,&nbsp;Julie Strizki,&nbsp;Arthur Fridman,&nbsp;Amanda Paschke,&nbsp;Carisa de Anda,&nbsp;Wei Gao,&nbsp;Matthew L. Rizk,&nbsp;Wendy Painter,&nbsp;Wayne Holman,&nbsp;Susanne Sardella,&nbsp;George Painter,&nbsp;Julie A. Stone","doi":"10.1111/cts.70184","DOIUrl":"https://doi.org/10.1111/cts.70184","url":null,"abstract":"<p>Molnupiravir, an orally administered drug for the treatment of mild-to-moderate COVID-19, is a prodrug of the ribonucleoside β-D-N4-hydroxycytidine (NHC). NHC incorporation in the SARS-CoV-2 RNA strand causes an accumulation of deleterious errors in the genome, resulting in reduced viral infectivity and replication. Exposure-response (E-R) analyses for viral RNA mutation rate and virologic outcomes were conducted using data from three phase 2/3 studies of molnupiravir (P006, MOVe-IN, and MOVe-OUT). Three dose levels (200, 400, and 800 mg every 12 hours [Q12H]) and placebo were evaluated. E-R datasets were generated for SARS-CoV-2 RNA mutation and longitudinal SARS-CoV-2 RNA viral load. E-R models were defined for RNA mutation rate and viral load change from baseline at days 5 and 10. The models supported plasma NHC AUC_0-12 as the appropriate pharmacokinetic driver for assessing E-R relationships. The highest percentage of participants with &gt; 20 low-frequency nucleotide substitutions (LNS) per 10,000 bases, a measure of likely meaningful drug effect, was predicted in the 800 mg Q12H treatment group. A strong drug effect on the reduction of viral load was observed on days 5 and 10. E-R relationships were best represented by an E_max structural model with reasonable consistency in the estimated AUC₅₀s (~2.3-fold), across the models, of 10,260 and 4390 nM*hr. for day 5 viral load change from baseline and LNS error rate, respectively. These biomarker E-R curves support the choice of 800 mg Q12H as providing near-maximal drug effect, consistent with findings from the previously published molnupiravir E-R model of clinical outcomes.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70184","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707209","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":"Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of ALXN1820 (Tarperprumig) in Healthy Adults: Results of a Phase I Study","authors":"Avner Sandhu,&nbsp;Tong Shen,&nbsp;Paz Martin Herrero,&nbsp;Chao-Xing Yuan,&nbsp;Samirah Qureshi,&nbsp;Xiaoyu Jiang,&nbsp;Ye Sheng,&nbsp;Christoph Gasteyger,&nbsp;Yang Dai","doi":"10.1111/cts.70190","DOIUrl":"https://doi.org/10.1111/cts.70190","url":null,"abstract":"<p>Properdin is an endogenous positive regulator of the complement alternative pathway (AP). Tarperprumig (ALXN1820), a novel humanized bispecific antibody, binds properdin and albumin and is being developed to treat complement-mediated diseases. This phase I, randomized, double-blind, placebo-controlled trial assessed the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and immunogenicity of tarperprumig in healthy adult participants. In cohorts 1 to 4 and 6, single doses of tarperprumig were administered via subcutaneous (SC) injection (12.5, 50, 150, 450, and 1200 mg doses). In cohorts 8 and 9, the 150 mg dose was given via SC injection once weekly for 5 doses. In cohort 5, a single dose of 450 mg was administered via intravenous infusion. Sixty participants were randomized (3:1) to tarperprumig or placebo. There were no discontinuations due to adverse events (AEs) in participants receiving tarperprumig. There were no serious AEs, events of serious infection, or deaths. No <i>N. meningitidis</i> infections occurred. Most AEs were mild and not treatment related. Tarperprumig exposure resulted in linear dose proportionality among all but one cohort. Mean absolute bioavailability of tarperprumig was 94%. AP activity decreased rapidly after tarperprumig administration. Complete AP inhibition (&lt; 1% of baseline value) was observed in all cohorts except for cohort 1 (12.5 mg SC). There was no change in complement classical or lectin pathway activity. Antidrug antibody titers were mostly low and did not impact PK. Tarperprumig was well tolerated and completely inhibited the AP in healthy adults. These results support continued investigation of tarperprumig to treat diseases involving complement activation.</p><p><b>Trial Registration:</b> EudraCT: 2021–002472-39/NCT04631562</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698895","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":"Investigation of the Molecular Mechanisms of Paraoxonase-2 Mediated Radiotherapy and Chemotherapy Resistance in Oral Squamous Cell Carcinoma","authors":"Mehta Vedant Kamal,&nbsp;Krishnananda Prabhu,&nbsp;Krishna Sharan,&nbsp;Ananth Pai,&nbsp;Sanjiban Chakrabarty,&nbsp;Rama Rao Damerla,&nbsp;Preethi S. Shetty,&nbsp;Vijetha Shenoy Belle,&nbsp;Mahadev Rao,&nbsp;Naveena A. N. Kumar","doi":"10.1111/cts.70201","DOIUrl":"https://doi.org/10.1111/cts.70201","url":null,"abstract":"<p>Oral squamous cell carcinoma (OSCC) is a common form of cancer, with 390,000 new cases estimated for 2022. OSCC has a poor prognosis, largely due to a high recurrence rate and resistance to therapy. Cancer cells develop resistance to standard therapy owing to various factors, such as genetic predispositions, alterations in the apoptotic pathway coupled with DNA repair pathways, drug efflux, and drug detoxification. This review is aimed at exploring the crucial role of paraoxonase 2 (PON2) in conferring resistance to chemotherapy and radiotherapy in OSCC cells. PON2, an antioxidant enzyme, protects cancer cells from the oxidative stress caused by these treatments. By influencing apoptotic pathways and DNA repair mechanisms, PON2 can reduce the effectiveness of therapy. This review is an attempt to explore the complex molecular mechanisms modulated by PON2, such as the mitigation of oxidative stress, enhancement of DNA repair, apoptosis regulation, drug efflux modulation, and drug detoxification, which decrease treatment efficacy.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70201","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698894","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}