Objective. To investigate whether synovial cells from rheumatoid arthritis (RA) synovium can be divided into 2 functionally different subpopulations: active or proliferative cells and apoptotic cells. Methods. Expression of cell surface and cyto-plasmic molecules on synovial cells was assessed by immunohistochemistry, flow cytometry, or Western blotting. Cells were categorized as intercellular adhesion molecule 1 (ICAM-1) positive or negative based on positive and negative selection of antibody-coated beads. Cell cycle and apoptosis were assessed using propidium iodide staining, TUNEL method, and DNA fragmentation. Results. Expression of ICAM-1 and Fas was noted mainly in the synovial lining to sublining layer in vivo, and synovial cells could be clearly distinguished as ICAM-1 positive or negative. The expression of Fas was higher on ICAM-1-positive cells than on ICAM-1-negative cells in vitro. The functional and phenotypic heterogeneity between ICAM-1-positive and-negative cells was further emphasized by cell cycle machinery. The majority of ICAM-1-positive cells were arrested at the G0/G1 phase, whereas many of the ICAM-1-negative cells were at the S to G2/M proliferating phase. In ICAM-1-positive cells, p53 and p21 expression was up-regulated and cyclin-dependent protein kinase 6 activity was inhibited. Most ICAM-1-positive cells were apoptotic (as evidenced by TUNEL positivity and DNA fragmentation). ICAM-1-positive cells were induced not only by interleukin-1, but also by Fas crosslinking. Conclusion. ICAM-1-positive synovial cells represent growth arrest and subsequent apoptosis, whereas ICAM-1-negative cells are proliferative. Such differences in regulation of the cell cycle based on ICAM-1 status are important determinants of the lifespan, proliferation , and growth arrest of RA synoviocytes.
Patients with ovarian serous carcinoma are generally diagnosed at an advanced disease stage. The standard treatment for these patients is maximal debulking surgery followed by platinum-taxane combination chemotherapy. Despite initially responding well, more than half of patients become refractory to first-line chemotherapy. Upregulation of protein arginine methyltransferase 1 (PRMT1) expression has been demonstrated to methylate apoptosis signal-regulated kinase 1 and inhibit its activity, thereby contributing to chemoresistance. The present study investigated the association between PRMT1 expression and sensitivity to platinum-based chemotherapy in 51 patients with ovarian serous carcinoma (International Federation of Gynecology and Obstetrics stages III and IV), and the effect of RNA interference-mediated downregulation of PRMT1 on the sensitivity of ovarian cancer cells to cisplatin and carboplatin in vitro. Immunohistochemistry of tumor specimens was used to compare the expression levels of PRMT1, a Cell Counting Kit-8 assay and small interfering RNA transfection were performed for chemosensitivity assays, and reverse transcription-quantitative PCR was used to examine PRMT1 mRNA expression. Patients were divided into platinum-sensitive (n=26) and platinum-resistant (n=25) groups. PRMT1 expression was significantly lower in the platinum-sensitive group than in the platinum-resistant group (P=0.019). When patients were categorized according to PRMT1 expression, those in the low PRMT1 expression group were more sensitive to platinum-based chemotherapy than those in the high PRMT1 expression group (P=0.01). Additionally, in vitro experiments revealed that suppression of PRMT1 expression by siRNA significantly increased the sensitivity of human ovarian serous carcinoma cells to cisplatin and carboplatin (P<0.05). In conclusion, PRMT1 expression could predict sensitivity to platinum-based chemotherapy in patients with ovarian serous carcinoma.
The standard care for patients with locally advanced cervical cancer is concurrent chemoradiotherapy. Successful neoadjuvant chemotherapy (NAC) can reduce tumor size and enable patients to be eligible for a hysterectomy, which can improve their prognosis. Selecting the right candidate for NAC is important since NAC failure results in switching to radiation therapy and can lead to a worse prognosis due to a delay in the initiation of the core therapy. Therefore, the identification of biomarkers that can predict the effect of NAC is essential. Previous reports have suggested a relationship between protein arginine methyltransferase (PRMT1) and chemoresistance in several types of cancer. PRMT1 has been demonstrated to methylate apoptosis signal-regulated kinase 1 and to inhibit its activity, thereby contributing to chemoresistance. The present study investigated the association between PRMT1 expression and the efficacy of NAC in locally advanced cervical cancer. Data from 53 patients with locally advanced uterine cervical cancer who were classified into two groups based on effective (n=28) and ineffective (n=25) responses to NAC treatment were evaluated. PRMT1 expression was investigated by immunohistochemistry and scored using a weighted scoring system. Additionally, the present study investigated the effect of RNA interference-mediated downregulation of PRMT1 on the sensitivity of cervical cancer cells to cisplatin in vitro . The results demonstrated that the NAC effective group had significantly lower weighted PRMT1 scores than the NAC ineffective group (P=0.030). In addition, lower tumor expression levels of PRMT1 were significantly associated with increased sensitivity to NAC (P=0.033). Furthermore, downregulation of PRMT1 expression in cervical cancer cells markedly improved their sensitivity to cisplatin in vitro . The present study suggested that PRMT1 expression has potential as a predictive marker of the efficacy of NAC in patients with locally advanced cervical cancer. This finding can contribute to improvements in the prognosis of these patients.
The role of the neutrophil-to-lymphocyte ratio (NLR) in predicting sensitivity to chemotherapy and prognosis has attracted great interest in several types of cancer. In the present study, the correlation between pre-chemotherapy NLR and sensitivity to platinum-based chemotherapy and prognosis in patients with advanced serous ovarian carcinoma was examined by retrospectively reviewing the medical records of 50 patients with stage III-IV serous ovarian carcinoma from 2005 to 2012. Patients were divided into high-NLR (32 patients) and low-NLR (18 patients) groups according to a cutoff value of 2.47. This cutoff was calculated using a receiver operating characteristic (ROC) curve that demonstrated 84% specificity and 60% sensitivity. Patient characteristics, sensitivity to platinum-based chemotherapy and prognosis were subsequently compared. The results revealed no significant difference in patient characteristics between the two groups. In the low-NLR group, 14 of 18 patients (77.8%) were sensitive to platinum-based chemotherapy, whereas 11 of 32 were sensitive in the high-NLR group (34.4%) (P=0.007). Overall and disease-free survival (DFS) were significantly longer in the low-NLR than in the high-NLR group (P=0.013 and P=0.043, respectively). The current results suggested that pre-chemotherapeutical NLR may serve as a biomarker of sensitivity to platinum-based chemotherapy and prognosis in patients with advanced serous ovarian carcinoma.
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