Knockdown of MPP8 suppresses cell proliferation via regulation of HOXA5 in non-small cell lung cancer cells.

M-phase phosphoprotein 8 (MPP8) is reported to be closely implicated in cancer initiation and progression. In addition, the homeobox gene HOXA5 has been shown to play critical roles in hematopoiesis, embryogenesis, and tumorigenesis. Nevertheless, the functional relevance of MPP8 and it's relation with HOXA5 in non-small cell lung cancer (NSCLC) is unknown. Therefore, the present study aimed to detect the expression profile of MPP8 in NSCLC and further explore it's biological roles in lung cancer cells. Cell proliferation was measured by CCK-8 assay and EdU incorporation assay. Real-time PCR was applied to detect the mRNA expression of MPP8 and HOXA5. The protein levels of MPP8 and HOXA5 were evaluated by western blot. Our study found that the expression of MPP8 was significantly increased in the NSCLC tissue compared with the adjacent non-tumorous tissue. Compared with the human lung fibroblasts, the elevated gene expression of MPP8 was also detected in the human NSCLC cell lines including NCI-H23 and NCI-H1299. In addition, knockdown of MPP8 led to an obvious reduction in cell viability and DNA synthesis in NCI-H23 and NCI-H1299 cells. Furthermore, down-regulation of MPP8 resulted in elevated expression of HOXA5 in NSCLC cells both at the mRNA and protein levels. Moreover, depletion of HOXA5 abolished the anti-tumor function of MPP8 knockdown in NSCLC cells. The present study demonstrated that MPP8 was associated with NSCLC cell proliferation through regulation of HOXA5, suggesting that MPP8 may act as a novel therapeutic target for treatment of NSCLC.

Impact of Intraoperative Blood Pressure Control and Temporary Parent Artery Blocking on Prognosis in Cerebral Aneurysms Surgery / 中国医学科学杂志(英文版)

Objective In cerebral aneurysm clipping and embolization, blood pressure control and temporary parent artery blocking are common methods to prevent aneurysm rupture. Their influence on the prognosis is uncertain. In this study, we try to find out the association between methods above and prognostic indicators.Methods We held a retrospective analysis on patients' medical records of cerebral aneurysms surgical clipping and endovascular coiling , and recorded gender, age, diagnosis, Hunt-Hess grade, Glasgow coma scale score, treatment methods, a history of hypertension, preoperative systolic blood pressure, with or without controlled hypotension, systolic blood pressure difference before and after controlled hypotension, with or without temporary artery blocking, with or without hypertension after treated aneurysm, prognostic indicators including mortality after 1 month, intensive care unit (ICU) stay time of survivors, discharged Glasgow outcome scale (GOS) score. Prognostic indicators were regarded as dependent variable, all the factors were regarded as independent variable, and the strength analysis of influence factors on prognostic indicators was made by binary logistic regression.Results Total cases were 165, including 68 males and 97 females, with an average age of 56 (12-85) years. The mortality after 1 month was 10.9% (18 cases). The ICU stay time of survivors was 7.35 (0-67) days. GOS score at discharge was 1-3 in 40 (24.2%) patients and 4-5 in 125 (75.8%) patients. Systolic blood pressure difference before and after controlled hypotension was an independent factor influencing mortality (t=2.273, P=0.024), and the greater the difference was, the higher the mortality would be. Timely hypertension after aneurysm treated was an independent factor affecting ICU stay time of survivors and patients with hypertension had shorter ICU stay time (χ=10.017, P=0.001). Blood pressure control (χ=0.088, P=0.767) and temporary blocking (χ=1.307, P=0.253) did not show significant influence on GOS score at discharge.Conclusions Timely controlled hypertension after aneurysm clipping and embolization can significantly shorten the stay time in ICU. The degree of controlled hypotension associates with postoperative mortality, the greater systolic blood pressure difference before and after antihypertensive treatment is, the higher the mortality will be.

Nerve growth factor expression in astrocytoma and cerebrospinal fluid: a new biomarker for prognosis of astrocytoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recent studies have discovered that nuclear translocation of nerve growth factor (NGF) and its receptor fragments function differently from the traditional model. This study aimed to uncover the nuclear expression of NGF in astrocytoma and its biological significance.</p><p><b>METHODS</b>Ninety-four paraffin-embedded astrocytoma specimens were subjected to immunohistochemical (IHC) and hemotoxylin & eosin (HE) staining. Preoperative cerebrospinal fluid (CSF) specimens and intraoperative snap-frozen astrocytoma tissues were assayed for NGF expression by ELISA and Western blotting. The outcome of patients who contributed samples was tracked. Each ten tissue samples from patients with traumatic brain injury who had received decompression surgery and CSF samples from patients undergoing spinal anesthesia but with no history of nervous system disease were taken as control.</p><p><b>RESULTS</b>NGF-positive immunoreactive products were distributed in both the cytoplasm and nucleus of astrocytoma, but were only located in the cytoplasm of traumatic brain injury (TBI) tissue. NGF nuclear-positive rate (NPR) of grades III - IV astrocytomas (70.0%) was higher than that of grades I - II astrocytoma (28.6%, P < 0.05). NGF-NP expression positively correlated with the NGF concentration in cerebrospinal fluid (CSF) (r = 0.755, P < 0.01). Kaplan-Meier survival analysis indicated that the median survival time was 25 months for NGF-NP astrocytoma grade I - II patients and 42 months in NGF nuclear negative (NGF-NN) astrocytoma grade I - II patients (P < 0.05). In astrocytoma III - IV patients, the median survival was 7 months for NGF-NP patients and 24 months for NGF-NN patients (P < 0.01). Two types of NGF with molecular weights of 13 and 36 kDa were present in astrocytoma, but only the 36 kDa NGF was found in the CSF. NGF expression elevated as the malignancy increased.</p><p><b>CONCLUSIONS</b>NGF-NP expression and NGF level in CSF were significant prognostic factors in astrocytoma patients. Because of the easy access of CSF, it may be developed as an index for early diagnosis and surveillance of astrocytoma.</p>