[Expression and correlation of CIP2A and OPN in bladder cancer].

OBJECTIVE: To explore the expressions of cancerous inhibitor of protein phosphatase 2A (CIP2A) and osteopontin (OPN) and evaluate their roles in bladder cancer. METHODS: RNA was isolated from 38 cases of patients with bladder cancer and 12 cases of normal bladder tissue by TRIzol method from May 2010 to December 2012. And reverse transcription (RT)-PCR was used to detect the expressions of CIP2A and OPN. The expression levels of CIP2A and OPN in 99 cases of patients with bladder cancer and 12 cases of normal tissue were detected by immunohistochemical staining. RESULTS: The positive expression rate of CIP2A mRNA and OPN mRNA were 76.32% (29/38) and 92.11% (35/38) in bladder cancer while there was no expression in normal tissue (both P < 0.05). The positive rates of CIP2A and OPN protein were 63.64% (63/99)and 84.85% (84/99)in cases of bladder cancer tissues while CIP2A was not detected in normal tissues. The positive expression rate of OPN in normal tissues was 2/12 (both P < 0.05). The CIP2A and OPN proteins were both expressed in 58/99 cases of bladder cancer tissues while neither of them was expressed in 13 cases. In 8 cases, CIP2A was expressed while OPN was not. In another 20 cases, OPN was expressed while CIP2A was not (r = 0.300, P < 0.05). CONCLUSIONS: The expression levels of CIP2A and OPN in tissue of bladder cancer are higher than those of normal controls. And CIP2A and OPN may be used as indicators of biological behaviors and serve as new molecular diagnostic markers for bladder cancer.

[Clinical significance of CIP2A expression in bladder cancer].

OBJECTIVE: To explore the expression of cancerous inhibitor of PP2A (CIP2A) and evaluate its role in bladder cancer. METHODS: RT-PCR was used to detect the expression of CIP2A mRNA from 38 cases of patients with bladder cancer and 12 cases of normal bladder tissue. The CIP2A protein expression levels in 99 cases of patients with bladder cancer and 12 cases of normal tissue was detected by immunohistochemical staining . And the serum contents of CIP2A protein of 38 patients with bladder cancer and 40 normal controls were detected by ELISA. RESULTS: The expression of CIP2A mRNA was detected in 29/38 cases (76.32%) of bladder cancer. And there was no expression in normal tissue (P < 0.05). The positive rate of CIP2A protein was 63.64% in 99 cases of bladder cancer tissues and no expression detected in normal tissues(P < 0.05). ELISA results showed that the serum content of CIP2A in patients with bladder cancer was significantly higher than that in normal controls (median:0.015 2 vs 0.001 8 ng/L, P < 0.05). CONCLUSIONS: The tissue and serum expressions of CIP2A in patients with bladder cancer are higher than those in normal controls. And CIP2A may be used as an indicator of the biological behavior of bladder cancer.

Omalizumab treatment and outcomes in Chinese patients with chronic spontaneous urticaria, chronic inducible urticaria, or both.

BACKGROUND: Chronic urticaria (CU) is a common skin disorder, which can be further divided into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Omalizumab is effective and safe for difficult-to-treat CSU based on clinical trials. However, there are limited data comparing the therapeutic effect of omalizumab for patients with CSU, CIndU, and CSU plus CIndU. Meanwhile, there is still no reliable predictor for treatment response or relapse. Our study was conducted to collect real-world clinical data on omalizumab treatment in patients with CSU, CIndU, and both. METHODS: This was an observational, retrospective chart review of patients with CU initiating omalizumab treatment between February 2018 and May 2020 (maximum 28 months follow-up). RESULTS: A total of 138 patients were included, 87 with CSU alone, 33 with different forms of CIndU, and 18 with both. A total of 87.0% (n = 120/138) of the CU patients responded to omalizumab therapy, among which 65.2% (n = 90/138) of the patients showed complete response and 21.7% (n = 30/138) of the patients showed partial response. The therapeutic effect and speed of onset of effect for omalizumab were comparable among patients with CSU, CIndU, or both. Autologous serum skin test (ASST)-positive patients were more likely to show a slow response to omalizumab therapy ( P  = 0.043). Non-responders had lower baseline total IgE levels (35.0 vs 121.5 kU/L, P  < 0.001). The proportion of patients with low total IgE levels in non-responders was significantly higher than that of responders (61.1% vs. 14.5%, P  < 0.001). Also, more non-responder patients had elevated thyroid autoantibodies than responders (50.0% vs. 23.0%, P  = 0.041). The median ratio of serum IgG-anti-TPO to serum total IgE in non-responders was significantly higher compared with responders (1.22 vs. 0.09, P  < 0.001). Non-responders also had shorter treatment periods (4.5 vs 6.0 months, P  = 0.035) compared with responders. Two of 3 patients (67.4%, n = 29/43) experienced relapse after ceasing omalizumab therapy. These patients had longer disease durations (52.0 vs. 15.0 months, P  = 0.007) and higher baseline total IgE levels (179.9 vs. 72.5 kU/L, P  = 0.020) than patients who did not relapse. We reinitiated omalizumab treatment for 10 relapsed patients, all of them reported a rapid response after the first injection within the first 4 weeks of retreatment. CONCLUSION: Omalizumab is highly effective in patients with difficult-to-treat CSU, CIndU, or both. Responders tend to have unique immunological features and longer treatment periods. Patients with higher baseline total IgE levels and longer disease durations are more likely to experience rapid relapse after discontinuation of omalizumab.

Progranulin protects against endotoxin-induced acute kidney injury by downregulating renal cell death and inflammatory responses in mice.

Progranulin (PGRN), a pluripotent secreted growth factor, is involved in various physiologic and disease processes. However, the role of PGRN in endotoxin-induced septic acute kidney injury (AKI) remains unknown. The objective of this study is to investigate the protective effects of PGRN on an endotoxin-induced AKI mouse model by using PGRN-deficient mice and recombinant PGRN (rPGRN) pretreatment. PGRN levels were increased in kidneys of wild-type (WT) mice at 6 and 24h after lipopolysaccharide (LPS) injection. Renal function detection, hematoxylin and eosin staining, immunohistochemical staining, ELISA and in situ terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick-end labeling were used to reveal tissue injury, inflammatory cell infiltration, production of inflammatory mediators and cell death in mouse kidneys after LPS injection. PGRN deficiency resulted in severe kidney injury and increased apoptotic death, inflammatory cell infiltration, production of pro-inflammatory mediators and the expression and nucleus-to-cytoplasmic translocation of HMGB1 in the kidney. In addition, rPGRN administration before LPS treatment ameliorated the endotoxin-induced AKI in WT mice. PGRN may be a novel biologic agent with therapeutic potential for endotoxin-induced septic AKI possibly by inhibiting LPS-induced renal cell death and inflammatory responses in mice.