Research Advances in Pituitary Adenoma and DNA Methylation.

DNA methylation is closely related to the genesis and development of pituitary adenoma. Studies have shown that high methylation in the promoter region of potassium voltage-gated chanel,shaker related subfamily,beta member 2,O-6-methylguanine-DNA methyltransferase,echinoderm microtubule associated protein like 2 ,ras homolog family member D ,homeobox B1 ,NNAT, and P16 inhibits the expression of these genes and regulates of the proliferation of pituitary adenoma. DNA methylation is also closely related to invasive pituitary adenoma. Therefore,further study on molecular mechanism of DNA methylation of pituitary adenoma will offer a new strategy for the diagnosis and treatment of pituitary adenoma.

[Diagnosis and Treatment of Pituitary Carcinoma].

The early diagnosis and treatment of pituitary carcinoma is difficult. The diagnosis is often delayed, and the confirmation of a diagnosis requires the presence of distant subarachnoid,brain or systemic metastasis from the primary pituitary tumor in the sella and also needs the evidences of pathology and imaging of the primary pituitary carcinoma and metastases. Treatment of pituitary carcinoma includes surgery, radiation therapy ,hormone therapy, chemotherapy, and molecularly targeted therapy; however, these methods are mainly palliative and can not prolong the survival. The prognosis remains poor. Efforts should be made to develop more effective diagnosis and treatment options.

[Treatment of pituitary adenomas invading cavernous sinus with neuroendoscopy assisted by multiple techniques].

OBJECTIVE: To study the effectiveness of treating giant pituitary adenomas invading cavernous sinus with neuroendoscopy assisted by multiple techniques. METHODS: A total of 72 patients who underwent neuroendoscopic surgery and 55 patients who underwent microscopic surgery for giant pituitary adenomas were enrolled in this retrospective analysis. Both groups received expanded endoscopic endonasal transsphenoidal approach, intraoperative application of navigation, and Doppler.The clinical data of two groups were compared. RESULTS: The two groups were significantly different in total tumor removal rate, operation time, postoperative nasal patency, and postoperative recurrence rate (P=0.004, P=0.0003, P=0.000, and P=0.002, respectively), whereas the cerebrospinal fluid leakage, postoperative diabetes insipidus, and cranial nerve injury were not significantly different (P > 0.05). CONCLUSIONS: Expanded neuroendoscopic endonasal transsphenoidal approach assisted by multiple techniques is the preferred surgical method for giant invasive pituitary adenomas invading cavernous sinus.The lateral cavernous sinus approach and the further molecular biology research will bring more options for the treatment of invasive pituitary adenomas.

Microsurgical treatment for parasagittal meningioma in the central gyrus region.

The aim of the present study was to determine the efficacy of microsurgery treatment for parasagittal meningioma in the central gyrus region. A microsurgical technique was used to treat 26 patients with large parasagittal meningioma in the central gyrus region. The Rolandic and draining veins and the peritumoral normal brain tissue were retained, and the associated sagittal sinus was appropriately protected. A Simpson grade I, II or III resection was performed in 8 (30.8%), 12 (46.2%) and 6 (23.1%) patients, respectively, with no post-operative mortalities. Following treatment, 9 patients exhibited hemiparalysis. No tumor recurrence was found in 21 patients during the follow-up examination. The treatment protocol described in the current study included sufficient pre-operative imaging evaluations, a skilled microsurgical technique, improved protection of the Rolandic vein and treatment of the sagittal sinus, and was found to significantly increase the total tumor removal rate and decrease post-operative recurrence.

Screening for AIP gene mutations in a Han Chinese pituitary adenoma cohort followed by LOH analysis.

OBJECTIVE: The aryl hydrocarbon receptor interacting protein gene (AIP) is associated with pituitary adenoma (PA). AIP has not been sequenced in East Asian PA populations, so we performed this study in a Han Chinese cohort. DESIGN: Our study included six familial PA pedigrees comprising 16 patients and 27 unaffected relatives, as well as 216 sporadic PA (SPA) patients and 100 unrelated healthy controls. METHODS: AIP sequencing was carried out on genomic DNA isolated from blood samples. Multiplex ligation-dependent probe amplification and microsatellite marker analyses on DNA from the paired tumor tissues were performed for loss of heterozygosity analysis. RESULTS: We identified three common and four rare single nucleotide polymorphisms (SNPs), one intron insertion, one novel synonymous variant, four novel missense variants, and a reported nonsense mutation in three familial isolated PA (FIPA) cases from the same family. Large genetic deletions were not observed in the germline but were seen in the sporadic tumor DNA from three missense variant carriers. The prevalence of AIP pathogenic variants in PA patients here was low (3.88%), but was higher in somatotropinoma patients (9.30%), especially in young adults (≤30 years) and pediatric (≥18 years) paients (17.24% and 25.00% respectively). All AIP variant patients suffered from macroadenomas. However, the AIP mutation rate in FIPA families was low in this cohort (16.67%, 1/6 families). CONCLUSION: AIP gene mutation may not be frequent in FIPA or SPA from the Han Chinese population. AIP sequencing and long-term follow-up investigations should be performed for young patients with large PAs and their families with PA predisposition.

Β-elemene inhibits Hsp90/Raf-1 molecular complex inducing apoptosis of glioblastoma cells.

ß-Elemene, an active component of herb medicine Curcuma wenyujin, has been shown to antagonize glioblastoma cells by inducing apoptosis. However, how ß-elemene induces apoptosis of these cells remains unclear. In this study, we report that ß-elemene disrupted the formation of the Hsp90/Raf-1 complex, a key step in maintaining the conformation stability of Raf-1, and caused deactivation of Raf-1 and inhibition of the ERK pathway, thereby leading to apoptosis of glioblastoma cells. Specifically, treatment of glioblastoma cell lines with ß-elemene attenuated phosphorylation of multiple members of the kinase families in the Ras/Raf/MEK/ERK cascade, including Raf-1 and ERK as well as downstream signaling targets such as Bcl-2. These results suggest that the Hsp90/Raf-1 complex could be a promising molecular target for new drug development for the treatment of glioblastoma.