Efficacy and safety of daratumumab in the treatment of relapsed/refractory multiple myeloma: A meta-analysis of randomized controlled trials.

BACKGROUND: Daratumumab as a monoclonal antibody has shown promising results in the treatment of relapsed/refractory multiple myeloma (RRMM). However, the efficacy and safety of daratumumab-based regimens compared to control regimens have not been fully established. METHODS: The search was conducted using electronic databases (PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials databases) up to December 2022. We conducted a meta-analysis of randomized controlled trials that evaluated the efficacy and safety of daratumumab in the treatment of RRMM. Data were extracted from eligible studies and were presented as hazard ratio or risk ratio (RR) with 95% confidence interval (CI). RESULTS: A total of 5 randomized controlled trials comprising 2003 patients were included in this meta-analysis. The results showed that daratumumab-based regimens significantly improved progression-free survival compared to control regimens (hazard ratio = 0.44, 95% CI 0.32-0.60, P < .00001). Additionally, daratumumab-based regimens significantly improved overall response rate compared to control regimens (RR = 1.25, 95% CI 1.16-1.36, P < .00001). the rate of minimal residual disease was also significantly higher in the daratumumab-based regimens (RR = 6.10, 95% CI 4.09-9.11, P < .00001). However, there was an increased risk of pneumonia, upper respiratory tract infections, and diarrhea in the daratumumab-based regimens. CONCLUSION: Our results suggest that daratumumab-based regimens are effective in the treatment of RRMM, improving progression-free survival, minimal residual disease, and overall response rate. However, there is an increased risk of pneumonia, upper respiratory tract infections, and diarrhea. Further studies are needed to determine the long-term safety and efficacy of daratumumab in the treatment of multiple myeloma.

PRL-3 and MMP9 Expression and Epithelial-Mesenchymal Transition Markers in Circulating Tumor Cells From Patients With Colorectal Cancer: Potential Value in Clinical Practice.

Objective: To evaluate the clinical correlation of epithelial-mesenchymal transition (EMT) with PRL-3 and MMP9 expression in the circulating tumor cells (CTCs) of patients with colorectal cancer (CRC). Materials and Methods: Between January 2016 and December 2018, the EMT phenotype-based subsets of CTCs and the expression levels of PRL-3 and MMP9 in CTCs were identified, and their clinical values in 172 patients were evaluated. The CTCs were isolated, classified, and counted using the CanPatrol™ CTC filtration system. The CTC subsets (epithelial cells, mesenchymal cells and biphenotypic cells), as well as PRL-3 and MMP9 expression, were detected by RNA in situ hybridization. Results: CTCs were detected in 93.0% (160/172) of the included patients with CRC. Positive PRL-3 and MMP9 expression in CTC and M-CTC was found in 75.0% (102/136) and 80.8% (97/120) of the patients, respectively. The proportion of patients with positive PRL-3 and MMP9 expression in M-CTC was significantly associated with distant metastasis (p<0.05). The patients with ≥6 CTCs tended to show poorer progression-free survival (PFS) and overall survival (OS) rates (p=0.016, 0.02, respectively), and the patients with ≥3 M-CTC also showed poor PFS (p=0.0013). Additionally, the patients with positive PRL-3 and MMP9 expression in CTCs had significantly poorer PFS (p=0.0024) and OS (p=0.095) than the patients with negative PRL-3 and MMP9 expression. Multivariate Cox analysis uncovered that positive PRL-3 and MMP9 expression in CTCs may be an independent prognostic factor for worse PFS. Conclusion: EMT phenotypes and CTC numbers can be used as prognostic indicators for metastasis and survival in patients with CRC, and the combination of PRL-3 and MMP9 expression in CTCs is a promising clinical marker for patients with CRC.

Using linked administrative and census data for migration research.

Migration is a core component of population change and is both a symptom and a cause of major economic and social phenomena. However, data limitations mean that gaps remain in our understanding of the patterns and processes of mobility. This is particularly the case for internal migration, which remains under-researched, despite being quantitatively much more significant than international migration. Using the Scottish Longitudinal Study, this paper evaluates the potential value of General Practitioner administrative health data from the National Health Service that can be linked into census-based longitudinal studies for advancing migration research. Issues relating to data quality are considered and, using the illustrative example of internal migration by country of birth, an argument is developed contending that such approaches can offer novel ways of comprehending internal migration, by shedding additional light on the nature of both movers and the moves that they make.

dTBC1D7 regulates systemic growth independently of TSC through insulin signaling.

The insulin signaling pathway plays key roles in systemic growth. TBC1D7 has recently been identified as the third subunit of the tuberous sclerosis complex (TSC), a negative regulator of cell growth. Here, we used Drosophila as a model system to dissect the physiological function of TBC1D7 in vivo. In mutants lacking TBC1D7, cell and organ growth were promoted, and TBC1D7 limited cell growth in a cell-nonautonomous and TSC-independent manner. TBC1D7 is specifically expressed in insulin-producing cells in the fly brain and regulated biosynthesis and release of insulin-like peptide 2, leading to systemic growth. Furthermore, animals carrying the dTBC1D7 mutation were hypoglycemic, short-lived, and sensitive to oxidative stress. Our findings provide new insights into the physiological function of TBC1D7 in the systemic control of growth, as well as insights into human disorders caused by TBC1D7 mutation.