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Byline: Shu-xin. Sun, Ji. Zhang, Ji-cheng. Sun, Zhi-jie. Chen, Xiang-heng. Zhang, Zheng-he. Chen, Jing-xiu. Huang, Yu. Jiang, Yong-gao. Mou, Zhong-ping. Chen, Ke. Sai Sir, A 51-year old man presented with [...]

Abstract Background Brain metastases (BM) from hepatocellular carcinoma (HCC) are extremely rare and are associated with a poor prognosis. The aim of this study was to define clinical outcome and prognostic determinants in patients with BM from HCC. Methods Between January 1994 and December 2009, all patients with HCC and BM treated in Sun Yat-sen University Cancer Center were retrospectively reviewed. Univariate and multivariate survival analyses were performed to identify possible prognostic factors. Results Forty-one patients were diagnosed with BM from HCC, an incidence of 0.47%. The median age at diagnosis of BM was 48.5 years. Thirty-three patients (80.5%) developed extracranial metastases at diagnosis of BM, and 30 patients (73.2%) had hepatitis B. Intracranial hemorrhage occurred in 19 patients (46.3%). BM were treated primarily either with whole brain radiation therapy (WBRT; 5 patients), stereotactic radiosurgery (SRS; 7 patients), or surgical resection (6 patients). The cause of death was systemic disease in 17 patients and neurological disease in 23. Patients in a high RPA (recursive partitioning analysis) class, treated with conservatively and without lung metastases, tended to die from neurological disease. Median survival after the diagnosis of BM was 3 months (95% confidence interval: 2.2-3.8 months). In multivariate analysis, the presence of extracranial metastases, a low RPA class and aggressive treatment, were positively associated with improved survival. Conclusions BM from HCC is rare and associated with an extremely poor prognosis. However, patients with a low RPA class may benefit from aggressive treatment. The clinical implication of extracranial metastases in HCC patients with BM needs further assessment.

Abstract Both intraparenchymal papillary meningioma and papillary meningioma with cyst formation of brainstem have never been reported. The authors present an extremely rare case of patient with intraparenchymal papillary meningioma of brainstem. A 23-year-old Chinese male presented with a 4-month history of progressive left upper limb and facial nerve palsy. Magnetic resonance imaging revealed a cystic-solid, heterogeneously enhancing mass in pons and right cerebral peduncle with no dural attachment. The tumor was totally removed via subtemporal approach. During surgery, the lesion was found to be completely intraparenchymal. Histological and immunohistochemical examinations were compatible with the diagnosis of papillary meningioma. The lesion recurred nine months after primary surgery, a second surgery followed by radiotherapy was performed. Till to now (nearly 2 years after the treatment), the patient is tumor free survival. Intraparenchymal meningioma of brainstem with cystic formation is very rare, however, it should be considered as a differential diagnosis of a brainstem neoplasm. The present case strongly recommended that postoperative radiotherapy was essential for the patients with papillary meningiomas.

The article presents a case study of a 51‑year old man, who was presented with a 5‑month history of acute pain bilaterally on the posterolateral aspect of his hip. It mentions that neurological examination revealed that the Lasegue sign was bilaterally positive, along with mild motor weakness. It mentions diagnosis of lumber nerve root cavernous angioma.

Background: Prolyl 4-Hydroxylase Subunit Alpha 1 (P4HA1) is the active catalytic component of prolyl 4-hydroxylase and plays a crucial role in modulating extracellular matrix hemostasis. P4HA1 has been reported to promote tumor progression by enhancing invasion and angiogenesis. Overexpression of P4HA1 is associated with decreased survival for patients with breast and prostate cancer. However, the prognostic significance of P4HA1 for glioma patients remains undefined., Methods: The expression of P4HA1 in 290 gliomas (WHO grade II-IV) and 10 normal brain tissues was examined with TMA-based immunohistochemistry assay. The correlation between P4HA1 expression and clinicopathological parameters as well as the prognosis of glioma patients was investigated., Results: Cytoplasmic expression of P4HA1 is high in 37.93% of all glioma cases, with 44.98% in high-grade gliomas and 19.75% in low-grade gliomas respectively. Increased P4HA1 level was correlated with advanced histological grade (p<0.01) and old age (p=0.01). Upregulation of P4HA1, as well as histological grade, was an independent risk factor for unfavorable prognosis. Subgroup analysis demonstrated that high P4HA1 expression was significantly associated with poor prognosis for high-grade gliomas (p<0.01) but not for low-grade gliomas., Conclusions: P4HA1 was upregulated in gliomas. High expression of P4HA1 was correlated with the malignancy of gliomas and could serve as a prognostic indicator for patients with high-grade gliomas., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Background: B7-H4, a member of the inhibitory B7 family, is shown to have a profound inhibitory effect on the proliferation, activation, cytokine secretion, and development of cytotoxicity of T cells and may be involved in immune evasion in cancer patients. Although B7-H4 expression has been detected in non-small cell lung cancer (NSCLC), there are no published reports on the expression of B7-H4 in brain metastases from NSCLC., Methods: We examined the expression of B7-H4 by immunohistochemistry in 49 cases of brain metastatic NSCLC, 18 cases of matched primary NSCLC, and 20 cases of NSCLC patients who had neither brain metastases nor other distant metastases., Results: B7-H4 was highly expressed in 20 (40.8%) out of 49 brain metastases and two (11.1%) out of 18 matched primary tumors. The expression of B7-H4 in brain metastases appeared to be significantly higher than their matched primary tumors (P = 0.016). We also found that patients with high B7-H4 expression in their primary NSCLC have a higher risk of developing brain metastases (P = 0.022). Univariate analyses showed that median overall survival was significantly shorter in patients with high B7-H4 expression in brain metastases (P = 0.002). Multivariate analyses showed that B7-H4 was a significant independent prognostic indicator (P = 0.003)., Conclusion: NSCLC patients with high B7-H4 expression may benefit from aggressive treatment and close surveillance. Furthermore, our study suggests that B7-H4 may play an important role in the metastatic process of NSCLC and is promising to be a new immune checkpoint molecule for future antitumoral immunotherapy.

Objective: To explore the survival of newly diagnosed malignant gliomas patients on combined modality therapy of surgery, radiotherapy and chemotherapy., Methods: The data of 122 newly diagnosed malignant glioma patients on combined modality therapy at our center between 2000 and 2010 were retrospectively reviewed and analyzed. The median age was 40 years old (range: 5 - 75) and median Karnofsky performance status score (KPS) 80 (range: 60 - 100). Combined modality therapy consisted of surgery (maximal safety tumor resection), followed by fractionated focal irradiation for a total dose of 54 - 60 Gy and then 4 - 6 cycles of adjuvant chemotherapy including temozolomide or nitrosourea-based regimens or other ones without temozolomide and nitrosourea. The overall and progression-free survivals were analyzed by the Kaplan-Meier method and the influencing factors screened by Cox proportional hazard model., Results: There were grade IV (n = 70) and grade III (n = 52). The median survival periods were 17.0 months for grade IV patients and 36.0 months for grade III ones. The 2, 3, 4 and 5-year survival rates were 32.0% vs 64.8%, 19.6% vs 47.8%, 11.8% vs 32.0% and 5.9% vs 25.4% (P < 0.01) for grades IV and III patients respectively. The median progression-free survivals were 9.0 vs 12.0 months and 1, 2 and 3-year progression-free survival rates 30.8% vs 50.0%, 12.3% vs 31.4% and 9.2% vs 17.7% (P < 0.01) respectively. Multivariate analysis revealed that histologic type was an independent prognostic factor., Conclusion: Combined modality therapy of surgery, adjuvant radiotherapy and chemotherapy may improve the survival of patients with malignant gliomas.

Tanshinone IIA is one of major constituents of Salvia miltiorrhiza Bunge known as Danshen. Our and others' studies have shown that Tan IIA could protect cardimyocyte against apoptosis; however the effect of Tan IIA on cardiac remodeling disease is still unknown. In this study, we investigated the effects of Tan IIA on cardiac hypertrophy and fibrosis in two-kidney, two-clip (2K2C) hypertensive rats and by which, if any, mechanisms. Administration of 2K2C hypertensive rats with Tan IIA attenuated cardiac dysfunction and fibrosis. However Tan IIA treatment had no effects on BP control. Further studies revealed that Tan IIA inhibited the increased NAD(P)H oxidase activity and expression as well as O2*- production in 2K2C hypertensive rats. Our results indicated that Tan IIA significantly improved cardiac function and attenuated fibrosis in 2K2C hypertensive rats. The protective action of Tan IIA is likely mediated by its antioxidant effect, independent of BP control, partially via inhibiting NADPH oxidase.

Aim: To investigate correlation between the expression of TGF-β1 and the amount of Treg cell in glioma, and evaluate their clinical values in predicting the prognosis of glioma., Methods: Double immunohistochemistry staining was used to detect the expression of TGF-β1, CD4 and Foxp3 in 135 specimens of human gliomas (WHO I 18, WHO II 45, WHO III 53, WHO IV 19) and 15 normal brain., Results: OF the 135 specimans of glioma, 58 showed low TGF-β1 expression and 77 (57.03%) showed high TGF-β1 expression while ws not expression in normal brain tissue. Average Treg cell density in glioma was 2. 031/HP, but there was no expression of Treg in normal brain tissue. Expression of TGF-β1 was positively correlated with the mount of Treg in glioma tissues (r = 0.294, P < 0.01). Compared with the low grade, The levels of TGF-β1 and the amount of Treg cells with significant higher in high-grade glioma, however the mount of Treg had no correlations with Sex, KPS score. The Laplan-Meier analysis showed that there wer significant difference in overall survival (OS) between the TGF-β1 high-expression and low-expression group (P < 0.001). Cox multivariate analysis showed that TGF-β1 and Treg were not independent prognostic factors (P > 0.05)., Conclusion: Intratumoral of TGF-β1 may relate to the infiltration of Treg cells in glioma tissues. The level of TGF-β1 was obviously increased in high grade. Glioma patients with TGF-β1 or Trg high expression have poorer prognosis, while TGF-β1 and Treg cannot serve as independent prognostic factors of glioma survival time.

Purpose: To determine whether mouse embryonic stem cell conditioned medium (ESC-CM) increases the proliferative capacity of human corneal endothelial cells (HCECs) in vitro., Methods: Primary cultures of HCECs were established from explants of the endothelial cell layer, including the Descemet's membrane. Cells were cultured in human corneal endothelium medium (CEM) containing 25% ESC-CM for the experimental group and CEM alone for the control group. Phase-contrast microscopy and reverse-transcription polymerase chain reaction (RT-PCR) were used to identify HCECs. The eruption time and HCEC morphology were observed under phase-contrast microscopy. We detected the protein expression of zona occludens protein-1 (ZO-1; a tight junction protein) and the Na(+)-K(+)-ATPase by western blot analysis and immunocytochemistry. The mRNA expression of the Na(+)-K(+)-ATPase, voltage-dependent anion channel 3 (VDAC3), solute carrier family 4, sodium bicarbonate cotransporter member 4 (SLC4A4), and chloride channel protein 3 (CLCN3) were detected by RT-PCR. To explore the proliferation capacity of HCECs, the colony forming efficiency (CFE) was determined by Giemsa staining and the cellular proliferation marker of Ki-67 protein (Ki-67) positive cells were detected by immunocytochemistry and flow cytometry. Progression of the cell cycle and apoptosis were analyzed by flow cytometry. Negative regulation of the cell cycle, as measured by cyclin-dependent kinase inhibitor p21 (p21) levels, was detected by western blot analysis and immunocytochemistry., Results: In primary culture, HCECs in the 25%ESC-CM group erupted with polygonal appearance on day 2, while those in the CEM group erupted with slightly larger cells on day 3-4. HCECs in the 25%ESC-CM group could be subcultured until passage 6 without enlargement of cell volume, while those in the CEM group were enlarged and lost their polygonal appearance by passage 2. HCECs in both the 25%ESC-CM and CEM groups expressed ZO-1, Na(+)-K(+)-ATPase, VDAC3, SLC4A4, and CLCN3. The number of Ki67 positive cells, CFE, and percentage of cells entering the S and G(2) phases were higher in the 25%ESC-CM group than in the CEM group. The number of apoptotic cells and p21 protein expression both decreased in the 25%ESC-CM group., Conclusions: Use of 25%ESC-CM significantly increased the number of proliferating cells. These effects may be achieved through inhibition of p21 expression and apoptosis. These results suggested that 25%ESC-CM may be a new tool for cultivating HCECs for transplantation.