PARP1 promotes EGFR-TKI drug-resistance via PI3K/AKT pathway in non-small-cell lung cancer.

PURPOSE: Tyrosine kinase inhibitor (TKI) resistance is the main type of drug resistance in lung cancer patients with epidermal growth factor receptor (EGFR) mutations, but its underlying mechanism remains unclear. The purpose of this work was to investigate the mechanism by which PARP1 regulates EGFR-TKI resistance to identify potential targets for combating drug resistance. METHODS: The GEO databases, TCGA databases, western blot and qPCR studies were used to investigate the expression of PARP1 in lung cancer cells and tissues and its correlation with the prognosis of lung cancer. The expression of PARP1 in lung cancer TKI resistant cell PC9-ER and TKI sensitive cell PC9 was analyzed by qPCR and western blot. After knocking down of PARP1, CCK-8 assays, colony formation, flow cytometry were used to investigate its impact on erlotinib sensitivity, cell survival, cell cycle, and apoptosis. RNA-seq was used to investigate the mechanism by which PARP1 participates in EGFR-TKI resistance, and the results were validated in vitro and in vivo studies. RESULTS: PARP1 was highly expressed in both lung cancer tissues and cells. Subsequently, increased PARP1 expression was observed in PC9-ER compared with its parental cell line. Knockdown of PARP1 increased erlotinib sensitivity, promoted cell apoptosis, and suppressed cell growth. RNA-seq and previous studies have shown that the PI3K/AKT/mTOR/P70S6K pathway is involved in PARP1-mediated TKI resistance, and these results were confirmed by Western blot in vitro and in vivo. CONCLUSION: PARP1 may serve as a potential therapeutic target for reversing EGFR-TKI resistance in NSCLC via the PI3K/AKT/mTOR/P70S6K pathway.

Microsurgery Resection of Intrinsic Insular Tumors via Transsylvian Surgical Approach in 12 Cases.

OBJECTIVE: To investigate the clinical characteristics, operative methods, and diffusion tensor imaging (DTI) in the resection of intrinsic insular gliomas via transsylvian approach. METHODS: From June 2008 to June 2010, 12 patients with intrinsic insular gliomas were treated via transsylvian microsurgical approach, with preoperative magnetic resonance imaging diffusion tensor imaging (MR DTI) evaluation. The data of these patients were retrospectively analyzed. RESULTS: All patients had astrocytoma, including 8 patients of Grades I to II, 2 patients of Grades III to IV, and 2 patients of mixed glial tumors. The insular tumors were completely removed in 9 patients, whereas they were only partially removed from 3 patients. No death was related to the operations. Two patients had transient aphasia, 2 experienced worsened hemiplegia on opposite sides of their bodies, and 2 had mild hemiplegia and language function disturbance. CONCLUSIONS: Most of the insular gliomas are of low grade. By evaluating the damage of the corticospinal tract through DTI and using ultrasonography to locate the tumors during operation, microsurgery treatment removes the lesions as much as possible, protects the surrounding areas, reduces the mobility rate, and improves the postoperative quality of life.

Expression of integrin-alpha(3) mRNA in meningiomas and its correlation with proliferation and invasion.

To investigate the expression of integrin-alpha3 mRNA in meningiomas and its correlation with proliferation and invasion, the expression of integrin-alpha(3) subunit was detected by using in situ hybridization in patients with meningiomas (36 cases) and normal dura (2 cases) and arachnoid tissues (2 cases). SABC immunohistochemical assay was used to study the expression of Ki-67 nuclear antigen. The results showed that the expression of integrin-alpha(3) mRNA in benign, atypical and malignant meningiomas was 2.52+/-0.362, 1.75+/-0.316 and 1.42+/-0.633, respectively. The expression levels of integrin-alpha(3) mRNA was significantly lower in atypical or malignant meningiomas than those in benign meningiomas (P<0.05, P<0.01, respectively). The expression of integrin-alpha(3) mRNA in those with invasive biological behavior was lower than that in those without invasion (1.63+/-0.462 vs. 2.61+/-0.526, P<0.01). Moreover, the expression of integrin-alpha(3) mRNA was inversely associated with Ki-67 labeling index in all cases. It suggested that integrin-alpha(3) subunit participated in the modulatory process of growth of meningiomas. The proliferation activity and malignant grade of meningiomas were increased with the decreased expression of integrin-alpha(3) subunit, and the down-regulation of integrin-alpha(3) mRNA was associated with the invasive biological behaviors in meningiomas.

Expression of Integrin-а3 mRNA in Meningiomas and Its Correlation with Proliferation and Invasion / 华中科技大学学报（医学）（英德文版）

To investigate the expression of integdn-а3 mRNA in meningiomas and its correlation hybridization in patients with meningiomas (36 cases) and normal dura (2 cases) and arachnoid tis-sues (2 cases).SABC immunohistochemical assay was used to study the expression of Ki-67 nuclear antigen.The results showed that the expression of integdn-a3 mRNA in benign,atypical and malig-nant meningiomas was 2.52i-0.362,1.75±0.316 and 1.42±0.633,respectively.The expression levels invasive biological behavior was lower than that in those without invasion (I.63±0.462 vs.Ki-67 labeling index in all cases.It suggested that integrin-a3 subunit participated in the modulatory process of growth of meningiomas.The proliferation activity and malignant grade of meningiomas

[Surgical treatment of patients with cerebral schistosomiasis].

Clinical data from 48 cases with cerebral schistosomiasis, who received surgery, were analyzed retrospectively. Surgical treatment was performed when the patient had the following conditions: mass focus confirmed by CT scanning, cranial hypertension, or ineffective drug therapy, or indistinguishable from glioma by iconographic diagnosis. Treatment of praziquantel was given when the patients got improved. Among the 48 patients with surgical treatment, 35 cases recovered, 8 showed an exacerbation of hemiparalysis, 5 had hemianesthesia, and epilepsy occurred in 2 cases, no cases died during or after the operation. Surgery combined with praziquantel therapy has been an effective way for the treatment of cerebral schistosomiasis.

[Expression of integrin-alpha 3 mRNA in meningiomas and its biological significance].

BACKGROUND & OBJECTIVE: It was reported that reported that changes of the expression of integrins played critical roles in differentiation, proliferation, and invasion of lung carcinoma, melanoma, and glioma. However, no data was available on the expression of integrins in meningiomas. The aim of this study was to investigate the expression of integrin-alpha 3 in meningiomas and its biological significance. METHODS: Integrin-alpha 3 subunit was detected using in situ hybridization in meningiomas(36 cases), normal dura(2 cases), and arachnoid tissue(3 cases). SABC immunohistochemical assay was used to determine the expressions of Ki-67 nuclear antigen. RESULTS: Expressions of integrin-alpha 3 mRNA in benign, atypical, and malignant meningiomas were 2.52 +/- 0.362, 1.75 +/- 0.316, and 1.42 +/- 0.633, respectively. The expression levels of integrin-alpha 3 mRNA were significantly lower in the atypical and malignant meningiomas than in the benign meningiomas(P < 0.05, < 0.01). The integrin-alpha 3 mRNA expression in those with invasive biological behavior was lower than that in those without invasion(1.63 +/- 0.462 vs 2.61 +/- 0.526, P < 0.01). Moreover, the expression of integrin-alpha 3 mRNA was inversely associated with Ki-67 labeling index. CONCLUSIONS: Integrin-alpha 3 sub-unit participates the process of regulating growth of meningiomas. The proliferational activity and malignant grade of meningiomas correlates to decreased expression of integrin-alpha 3 subunit, and the down-regulation of integrin-alpha 3 mRNA is associated with the invasive biological behavior in meningiomas.