Efficacy and Safety of Pembrolizumab Monotherapy or Combined Therapy in Patients with Metastatic Triple-negative Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Review

作者: Mousavi, Tahoora ; Alimohammadi, Mina ; Araghi, Mahmood ; Soleimantabar, Hussein ; Mafi, Alireza ; Gharebakhshi, Farshad ; Faramarzi, Fatemeh

Background:Metastatic Triple-negative Breast Cancer (mTNBC) is the most aggressive form of breast cancer, with a greater risk of metastasis and recurrence. Research studies have published in-depth analyses of the advantages and disadvantages of pembrolizumab, and early data from numerous trials suggests that patients with mTNBC have had remarkable outcomes. This meta-analysis compares the data from numerous relevant studies in order to evaluate the safety and efficacy of pembrolizumab monotherapy or combination therapies for mTNBC.Methods:To identify eligible RCTs, a thorough literature search was carried out using electronic databases. CMA software was utilized to perform heterogeneity tests using fixed and random-effects models.Results:According to our pooled data, the median Progression-free Survival (PFS) was 2.66 months, and the median overall survival (OS) was 12.26 months. Furthermore, by comparing efficacy indicators between PD-L1–positive and PD-L1–negative groups, a correlation was found between the overexpression of PD-L1 with OS, PFS, and ORR. Patients with PD-L1-positive tumors had a higher response rate, with an ORR of 21.1%, compared to the patients with PD-L1-negative tumors. The ORR for first-line immunotherapy was higher than that of ≥second-line immunotherapy. In addition, pembrolizumab plus combination treatment resulted in a pooled incidence of immune- related adverse events of 22.7%.Conclusion:A modest response to pembrolizumab monotherapy was detected in the mTNBC patients. Furthermore, a better outcome from pembrolizumab treatment may be predicted by PD-L1-- positive status, non-liver/lung metastases, combination therapy, and first-line immunotherapy. Pembrolizumab, in combination with chemotherapy, may be more beneficial for patients whose tumors are PD-L1 positive.

2024-12-01·Molecular Genetics and Genomics

Identification of four novel mutations in VSP13A in Iranian patients with Chorea-acanthocytosis (ChAc)

Article

作者: Dadfar, Mahdi ; Rahimi, Hamzeh ; Ghoreishi, Abdoreza ; Ghodsinezhad, Vadieh ; Rostami, Ali ; Mohammadzadeh, Akbar ; Rohani, Mohammad

Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder characterized by a variety of involuntary movements, predominantly chorea, and the presence of acanthocytosis in peripheral blood smears. ChAc is caused by mutations in the vacuolar protein sorting-associated protein 13A (VPS13A) gene. The aim of the present study was to conduct a clinical and genetic analysis of five patients with suspected ChAc in Iran. This study included five patients who were referred to the genetic department of the Endocrinology and Metabolism Research Institute between 2020 and 2022, with a suspicion of ChAc. Clinical features and the presence of characteristic MRI findings were evaluated in the patients. Whole-exome sequencing (WES) followed by Sanger sequencing was employed to identify the disease-causing variants. The functional effects of novel mutations were analyzed by specific bioinformatics prediction tools. WES and data analysis revealed the presence of five distinct VPS13A mutations in the patients, four of which were novel. These included one nonsense mutation (p.L984X), and three splice site mutations (c.755-1G>A, c.144+1 G>C, c.2512+1G>A). All mutations were validated by Sanger sequencing, and in silico analysis predicted that all mutations were pathogenic. This study provides the first molecular genetic characteristics of Iranian patients with ChAc, identifying four novel mutations in the VPS13A gene. These findings expand the VPS13A variants spectrum and confirm the clinical variability in ChAc patients.

2024-12-01·Psychoneuroendocrinology

Investigating the bacterial profiles of Lactobacillus, Bifidobacterium, Actinobacteria, Fusobacterium, Firmicutes, and Bacteroides in stool samples from patients with severe depression and healthy individuals

Article

作者: Arbabi, Fatemeh ; Shapoury, Reza ; Zeighami, Habib ; Pirzeh, Reza ; Haghi, Fakhri

Depression is a multifaceted mental health disorder with complex etiology and significant global burden. Recent research indicates that the gut microbiota plays a role in the pathophysiology of depression, highlighting the potential role of specific bacterial species in influencing mood and cognitive function. In this study, we aimed to investigate the presence, copy numbers, and Ct values of selected bacterial species in stool samples from depressed patients (n=50) compared to control subjects (n=50). Our findings revealed significant differences in the abundance of Fusobacterium spp., Bifidobacterium spp., Lactobacillus spp., Bacteroidetes phylum, Firmicutes phylum, and Actinobacteria spp. between the two groups. Dysregulation of the gut microbiota, characterized by decreased presence of beneficial bacteria (e.g., Bifidobacterium spp., Lactobacillus spp.) and altered abundance of potentially pathogenic bacteria (e.g., Fusobacterium spp.), may contribute to the development or exacerbation of depression. These findings support the emerging concept of the gut-brain axis and its role in mental health. However, further research is needed to better understand the underlying mechanisms and explore the therapeutic potential of microbiota-targeted interventions for depression. Understanding the intricate interplay between the gut microbiota and depression could pave the way for novel treatment strategies and personalized approaches in mental health care.

100 项与 Zanjan University of Medical Sciences 相关的药物交易

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100 项与 Zanjan University of Medical Sciences 相关的转化医学

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