International journal of clinical pharmacology and therapeutics最新文献

The high incidence of malignant tumors continues to pose a significant threat to public health. In recent years, there have been notable advancements in tumor treatment methods, leading to substantial changes in the concepts and clinical approaches to treatment. The primary clinical methods for treating malignant tumors currently include surgical resection, radiation therapy, and chemotherapy. Among these, chemotherapy is one of the most crucial and comprehensive treatment strategies. The rapid progress in nanoscience has fostered the development of nanocarrier compounds and their clinical applications in disease treatment. Notably, nanomedicines, including goserelin sustained-release implants, doxorubicin liposomes, albumin-bound paclitaxel, and paclitaxel liposomes, have been effectively utilized in tumor treatment in China [1]. The article presents a comprehensive overview of recent advancements in utilizing various nanocarriers for combination therapy in tumors. It also examines the clinical application and efficacy of drug delivery carriers. The development of efficient and safe co-delivery systems that facilitate the effective transport and precise release of drugs within the cancerous tissues while also elucidating the internalization of nanoparticles into tumor cells and their functional mechanisms represents critical areas for future research. Concurrently, advancements in nanocarriers and tumor treatment are anticipated to yield superior therapeutic outcomes and improved quality of life for cancer patients.

Background: Bone-related disorders pose significant challenges in clinical practice. Bone marrow mesenchymal stem cells (BMSCs), as multipotent stem cells, play a pivotal role in bone regeneration. The TGF-β1-Smad2/3 signaling pathway is a well-recognized regulator of BMSC osteogenic differentiation. Traditional Chinese medicine (TCM), such as Bushen Tian Sui decoction (BSTSD), has shown potential in enhancing bone health; however, its molecular mechanisms remain poorly understood.

Objective: Investigating the effects and underlying mechanisms of BSTSD on the osteogenic differentiation of BMSCs.

Materials and methods: The impact of BSTSD on BMSCs was comprehensively analyzed using Cell Counting Kit-8 (CCK8), quantitative polymerase chain reaction (qPCR), western blot (WB), and immunofluorescence assays.

Results: CCK8 results revealed the highest optical density (OD) values in the BSTSD + activator group at 24, 48, and 72 hours, indicating enhanced cell proliferation. qPCR analysis showed significantly increased expression levels of TGF-β1, Smad2, Smad3, SOX9, and RUNX2 in the BSTSD + activator group, suggesting a synergistic effect in promoting osteogenic and chondrogenic differentiation. WB results demonstrated elevated phosphorylation levels of Smad2 and Smad3 (p-Smad2, p-Smad3) in the BSTSD + activator group, while total Smad2 and Smad3 protein levels remained consistent among groups. Immunofluorescence assays confirmed the highest fluorescence intensity, positive area ratio, and cell count containing Smad2 and Smad3 proteins in the BSTSD + activator group, validating the synergistic effect of BSTSD and TGF-β1.

Conclusion: BSTSD exhibits promising effects on BMSC differentiation and bone regeneration, mediated through the TGF-β1-Smad2/3 signaling pathway.

Background: Colorectal cancer (CRC) is a malignant tumor with the third highest incidence worldwide. The comprehensive economic evaluation of programmed cell death protein-1 inhibitors in China, however, has not yet been carried out. The aim of this study is to assess the cost-utility of pembrolizumab and nivolumab in the treatment of metastatic colorectal cancer (mCRC).

Materials and methods: A Markov model microsimulation of efficacy and cost-utility analysis (CUA) was carried out, and efficacy and safety data were compared using network meta-analysis. Literature screening and data extraction were performed according to established criteria where the main outcome indicators, complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were compared between two treatments. The lifetime cost and outcomes of mCRC treatment were estimated, and quality-adjusted life years (-QALYs) and incremental cost-effectiveness ratio (ICER) were used to evaluate the economy of each program.

Results: A total of 442 studies were evaluated of which 15, with a total of 798 patients, were included in the analysis. Of these, 13 evaluated PD, and total patients for CR, PR, SD, and PD were 82, 283, 160, and 180 respectively. The corresponding heterogeneity values were (p = 0.13, heterogeneity index as percentage (I²) = 29.53%), (p < 0.01, I² = 72.55%), (p = 0.03, I² = 46.54%), (p < 0.01, I² = 80.31%), and (p = 0.13 > 0.05). The proportion of patients classified as CR in the pembrolizumab group was greater than in the nivolumab group (0.105 vs. 0.085). However, the number of patients classified as PR and SD in the nivolumab group exceeded those in the pembrolizumab group. The number of patients classified as PD were similar in the two groups. Combination therapy nivolumab + ipilimumab yielded an incremental gain of 0.04 QALYs at an additional cost of 356,723 ¥. The ICER reached 8,918,075 ¥/QALYs, surpassing three times the per capita gross domestic product (GDP).

Conclusion: Both pembrolizumab and nivolumab showed beneficial effects in patients with mCRC. Nivolumab in combination with ipilimumab led to improved progression-free survival, but the values for ICER reached 8,918,075 ¥/QALYs. Treatment of non-resectable or metastatic microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) advanced solid tumors CRC with pembrolizumab alone, in the Chinese population examined, was the most cost-effective, where the willingness-to-pay threshold was 242,928 ¥/QALY (100 ¥ = 13.75 US$ and 12.63 €).

A characteristic toxicity of niraparib is a decrease in blood platelets (PLT), with an incidence of ~ 34% for grades 3 - 4 conditions. However, exceedingly severe cases have been reported infrequently. This paper describes three patients with acute and refractory severe PLT deficiency due to niraparib administration. The symptom characteristics, treatment course, and outcomes have also been analyzed, and the potential for the involvement of immune-related factors is considered. Therefore, it is recommended to comprehensively assess bone marrow hematopoietic function and high-risk variables before administering niraparib, intensify self-management and monitoring of patients, track changes in indicators, and intervene promptly. Additionally, if standard PLT-elevating therapies are ineffective, early full-dose administration of thrombopoietin receptor agonists, preferably avatrombopag, may be beneficial for reversing PLT loss of control.

Objective: This study aimed to detect cardiovascular disease-related signals using Global Individual Case Safety Report data on JAK inhibitors.

Materials and methods: A signal detection study was conducted using the WHO-UMC VigiBase.

Results: This study identified four cardiovascular adverse event signals associated with JAK inhibitors in Asian populations, including pulmonary embolism, deep vein thrombosis, thrombosis, and cerebrovascular accidents.

Conclusion: Analysis of Asian populations revealed a higher risk of thromboembolic events associated with JAK inhibitors than with TNF inhibitors. However, unlike in the Western populations, no myocardial infarction signal was detected in the Asian populations.

Introduction: Sunitinib is an oral drug approved for the treatment of metastatic renal cell carcinoma. Serious cutaneous adverse reactions to sunitinib are rare, and when they occur, discontinuation of the treatment may be needed.

Case report: A 70-year-old male patient was diagnosed with stage IV clear cell renal carcinoma and received treatment with sunitinib. After a second cycle with a 25% dose reduction, the patient was admitted with a diagnosis of grade 3 genital erythema. After ruling out other common causes, sunitinib was considered the cause of genital erythema and was stopped. Treatment with corticosteroids, topical applications, and morphine was started, with resolution after 18 days of evolution.

Discussion: There are only a few published reports that describe erythema and scaling of the genital skin. As in those few cases, for our patient, the first clinical signs appeared on day 28 of sunitinib treatment, and the lesions disappeared after 2 weeks without the use of the drug. Erythema and scaling reappeared when the drug was reintroduced, with greater severity than what was described in some of the other cases, which even included cases for which the lesions did not reappear.

Conclusion: Rare instances of severe and limiting skin toxicity may necessitate treatment suspension and compromise survival, as observed in our case. It is crucial to recognize these skin toxicities and understand their appropriate management strategies to initiate treatment as early as possible, thereby avoiding hospitalizations and enabling the resumption of sunitinib therapy.