The ARF6 GTPase is essential for regulating multiple cellular processes, such as, secretion, endocytosis, membrane trafficking, cell migration. ACAP4 is an ARF6 GTPase‐activating protein is critical EGF‐elicited cell migration (Mol. Cell Proteomics. 5, 1437‐49). However, how ACAP4 regulates proper levers of active ARF6 is not well understood. Here we show that, arrestin domain‐containing 5 (ARRDC5), a novel protein of α‐ arrestin family, competes with ARF6 for binding ACAP4. ARRDC5 can inhibit ACAP4 mediated inactivation of ARF6 in a dose‐dependent manner. Knock‐down of ARRDC5 decreases cellular ARF6‐GTP, whereas ARRDC5 overexpression increases cellular ARF6‐GTP. Surprisingly, EGF stimulation of cells causes phosphorylation of ARRDC5 at Ser247 by AKT1, which is essential for cell motility. Significantly, our biochemical characterization demonstrated that the phosphorylation of Ser247 strengthens ACAP4‐ARRDC5 association. The co‐localization of ACAP4 with ARRDC5 occurred in ruffling membranes formed upon EGF stimulation. In addition, expression of the phospho‐mimicking mutant of ARRDC5 promotes ARF6 activation and cell migration, knock‐down of AKT1 inhibits ARF6 activation and cell migration. Our date thus uncover ARRDC5 as a modifier of cellular ARF6‐GTP through regulation of ACAP4. AKT1‐mediated ARRDC5 phosphorylation facilitates cell migration by sequestering ACAP4 at the cell membrane to stabilize active ARF6 in response to EGF stimulation. Grant Funding Source : DK56292
The phase transition behaviors of the shocked water are investigated by employing an optical transmittance in-situ detection system. Based on the light scattering theory and phase transformation kinetics, the phase transition mechanism of the water under multiple shocks is discussed. The experimental data indicate that the evolution of the transmittance of the shocked water can be broadly divided into three stages: relaxation stage, decline stage, and recovery stage. In the early stage of the phase transition, the new phase particles began to form around the quartz/window interface. It should be mentioned that the water/ice phase boundary seems to move toward the liquid region in one experiment of this work. Due to the new phase core being much smaller than the wavelength of the incident light, the transmittance of the sample within the relaxation stage remains steady. The decline stage can be divided into the rapid descent stage and the slow descent stage in this work, which is considered as the different growth rates of the new phase particle under different shock loadings. The recovery stage is attributed to the emergence of the new phase particles which are bigger than the critical value. However, the influence of the size growth and the population growth of the new phase particles on the transmittance restrict each other, which may be responsible for the phenomenon that the transmittance curve does not return to the initial level.
A scientific and comprehensive analysis of the current status and trends in the field of cancer-associated fibroblast (CAF) research is worth investigating. This study aims to investigate and visualize the development, research frontiers, and future trends in CAFs both quantitatively and qualitatively based on a bibliometric approach.A total of 5518 publications were downloaded from the Science Citation Index Expanded of Web of Science Core Collection from 1999 to 2021 and identified for bibliometric analysis. Visualized approaches, OriginPro (version 9.8.0.200) and R (version 4.2.0) software tools were used to perform bibliometric and knowledge-map analysis.The number of publications on CAFs increased each year, and the same tendency was observed in the RRI. Apart from China, the countries with the largest number of publications and the most cited frequency were mainly Western developed countries, especially the USA. Cancers was the journal with the largest number of articles published in CAFs, and Oncology was the most popular research orientation. The most productive author was Lisanti MP, and the University of Texas System was ranked first in the institutions. In addition, the topics of CAFs could be divided into five categories, including tumor classification, prognostic study, oncologic therapies, tumor metabolism and tumor microenvironment.This is the first thoroughly scientific bibliometric analysis and visualized study of the global research field on CAFs over the past 20 years. The study may provide benefits for researchers to master CAFs' dynamic evolution and research trends.
// Xuefei Sun 1, * , Jing Liu 1, * , Yaming Wang 2 , Xueyan Bai 1 , Yuedan Chen 1 , Jun Qian 1 , Hong Zhu 1 , Fusheng Liu 3 , Xiaoguang Qiu 4 , Shengjun Sun 5 , Nan Ji 6 and Yuanbo Liu 1 1 Department of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 2 Department of Neurosurgery, Navy General Hospital, Beijing, China 3 Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 4 Department of Radiation Therapy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 5 Neuroimaging Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 6 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China * These authors contributed equally to this work Correspondence to: Yuanbo Liu, email: yuanbol@ccmu.edu.cn Keywords: primary central nervous system lymphoma, rituximab, high-dose methotrexate, cytarabine, survival Received: December 21, 2016 Accepted: April 02, 2017 Published: April 13, 2017 ABSTRACT Purpose: High-dose methotrexate based chemotherapy is the standard treatment for patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The role of rituximab is controversial because of its large size, which limits its penetration of the blood-brain barrier. In this study, we investigated the efficacy and tolerability of adding rituximab to methotrexate-cytarabine-dexamethasone combination therapy (RMAD regimen). Results: The patients treated with RMAD had a complete remission rate of 66.7% after induction chemotherapy; this rate was only 33.3% in patients treated with MAD alone ( p = .011). The most common grade 1–3 adverse events were similar and included hematologic toxicity, increased aminotransferase levels, and gastrointestinal reactions. Multivariate analysis revealed that rituximab treatment was associated with longer progression-free survival (PFS, p = .005) but not overall survival (OS). Additionally, we observed that elevated serum lactate dehydrogenase was associated with shorter OS and PFS. Materials and Methods: We retrospectively analyzed 60 immunocompetent patients with newly diagnosed PCNSL at Beijing Tiantan Hospital, Capital Medical University from January 2010 to June 2016. Twenty-four patients received 3–6 courses of 3.5 g/m 2 methotrexate on day 1; 0.5–1 g/m 2 cytarabine on day 2; and 5–10 mg dexamethasone on days 1, 2 and 3. Thirty-six patients received the same combination plus rituximab 375 mg/m 2 on day 0. All patients repeated the treatment every 3 weeks. Conclusions: High-dose methotrexate based chemotherapy with rituximab yields a higher complete remission rate and does not increase serious toxicities. PFS benefits from the addition of rituximab. OS has an increasing trend in patients treated with rituximab without statistical significance.
Objective: To investigate the mechanism of resistance and reversal effect of ligustrazine and cyclosporin A in cisplatin-induced multidrug resistance ovarian cancer cell line 3Ao/cDDP. Methods: Using the corresponding dose calculated from clinical chemotherapy at 30 mg cisplatin per cycle, we established 3Ao/cDDP with 3Ao exposed at regular intervals and repeatedly to high-level concentration of cisplatin at 10 µg/ml for 24 hours each time. Expressions of LRP, MRP, P-gp, GSTπ and TopoII were quantitatively detected with FCM. For drug resistance reversal, cyclosporin A and ligustrazine were administered singly or in combination at the maximal dose without cytotoxicity. Inhibition rates were determined by MTT assay. Results: 3Ao/cDDP was established after 4.5 months, with resistance factor 1.6 which was similar to clinical resistance degree. Low expression levels of MRP and P-gp were found in both 3Ao and 3Ao/cDDP (P>0.05), and LRP and GSTπ expression levels in 3Ao/cDDP were significantly higher than those in 3Ao (P<0.005 andP<0.05, respectively), and TopoII in 3Ao/cDDP was significantly lower vs 3Ao (P<0.05). The inhibition rate of cDDP was 20.807±0.015%, cDDP plus ligustrazine 27.421±0.07% (P>0.05 vs cDDP), cDDP plus cyclosporin A 49.635±0.021% (P<0.01 vs cDDP), and cDDP plus ligustrazine and cyclosporin A 58.861±0.014% (P<0.01 vs cDDP). Conclusions: 3Ao/cDDP, induced by cisplatin and established by imitating the characteristics of clinical chemotherapy for epithelial ovarian cancer, was an ideal model for investigation of cisplatin resistancein vitro. Cisplatin resistance in 3Ao/cDDP could be accounted for by higher LRP, GSTπ and lower TopoII expression and was not associated with MRP or P-gp. Ligustrazine had no significant reversal effect on cisplatin resistance, but cyclosporin A could reverse the resistance effectively.
To the Editor: Chordoma is a rare and aggressive bone tumor. This tumor has a high local recurrence rate and poor clinical outcomes. The study of the survival prognosis of chordoma is of great significance. Recently, we read with great interest the article by Passeri et al1 on a new predictor of chordoma. In this article, the authors performed a retrospective study of the relationship between tumor progression-free survival (PFS) and the tumor growth rate (TGR) in 32 patients with chordoma. They found that the higher TGR value (≥10.12) predicts worse PFS, and TGR can be regarded as a new predictor of PFS. We appreciate the authors for this meaningful study because these useful results would be helpful to adjust the prognostic stratification and clinical decision making. However, there are some remarks to communicate with the authors. First, some selection bias may be present in this article. The authors included only the patients with chordoma who had undergone 2 or more preoperative MRI scans with an interval of at least 2 mo between them. Clinically, however, the rapid growth of tumors in a short period of time to produce the symptoms of the case is not rare. In this situation, the review of the MRI may be necessary. In addition, some of the patients included had undergone surgery and radiation therapy, and these chordomas may themselves be more prone to recurrence. Studies have shown that dedifferentiated chordoma can be classified as de novo or secondary, and secondary chordoma usually occurs after radiotherapy or recurrence after surgery, which has a more aggressive clinical progression and a poorer prognosis compared with classical chordoma.2,3 Second, whether the tumor infiltrates surrounding tissues should be considered. Radical resection will be difficult if the tumor invades vital blood vessels, nerves, muscles, or brain tissue. Previous studies have shown that chordoma invades muscles and sacroiliac joints, which are associated with higher recurrence rates and poorer outcomes.4-6 Third, the initial size of the mass should be quantified. Different sizes of lumps may have different biological behaviors. Kayani et al4 found that lump size larger than 10 cm in diameter may be associated with increased local recurrence and mortality in patients with chordoma. It may be related to the difficulty of complete resection of the mass. In addition, the TGR of different initial mass sizes and its effect on prognosis can be investigated. Finally, it is necessary to understand the underlying mechanisms in different tumor growth rates. According to the authors' results, patients with chordoma could be divided into 2 groups (TGR ≥ 10.12%/m, or TGR < 10.12%/m) to compare the differences in cell composition between them. Zou et al7 found that the stromal content would be associated with patients' outcomes and the low tumor–stroma ratio predicts a worse prognosis. Furthermore, cancer stem cells8 are also worth investigating in the 2 groups. In conclusion, the authors' results are very beneficial for adjusting treatment strategies for patients with chordoma, but it needs to be confirmed by well-designed studies with a larger sample size.
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