Relationship of calcitonin gene-related peptide with disease progression and prognosis of patients with severe traumatic brain injury.

Calcitonin gene-related peptide (CGRP) has been implicated in multiple functions across many bioprocesses; however, whether CGRP is associated with severe traumatic brain injury (TBI) remains poorly understood. In this study, 96 adult patients with TBI (enrolled from September 2015 to December 2016) were divided into a mild/moderate TBI group (36 males and 25 females, aged 38 ± 13 years) and severe TBI group (22 males and 13 females, aged 38 ± 11 years) according to Glasgow Coma Scale scores. In addition, 25 healthy individuals were selected as controls (15 males and 10 females, aged 39 ± 13 years). Radioimmunoassay was used to detect serum levels of CGRP and endothelin-1 at admission and at 12, 24, 48, 72 hours, and 7 days after admission. CGRP levels were remarkably lower, but endothelin-1 levels were obviously higher in the severe TBI group compared with mild/moderate TBI and control groups. Levels of CGRP were remarkably lower, but endothelin-1 levels were obviously higher in deceased patients compared with patients who survived. Survival analysis and logistic regression showed that both CGRP and endothelin-1 levels were associated with patient mortality, with each serving as an independent risk factor for 6-month mortality of severe TBI patients. Moreover, TBI patients with lower serum CGRP levels had a higher risk of death. Thus, our retrospective analysis demonstrates the potential utility of CGRP as a new biomarker, monitoring method, and therapeutic target for TBI.

ROS-p53-cyclophilin-D signaling mediates salinomycin-induced glioma cell necrosis.

BACKGROUND: The primary glioblastoma multiforme (GBM) is the most malignant form of astrocytic tumor with an average survival of approximately 12-14 months. The search for novel and more efficient chemo-agents against this disease is urgent. Salinomycin induces broad anti-cancer effects; however, its role in GBM and the underlying mechanism are not clear. RESULTS: Here we found that salinomycin induced both apoptosis and necrosis in cultured glioma cells, and necrosis played a major role in contributing salinomycin's cytotoxicity. Salinomycin induced p53 translocation to mitochondria, where it formed a complex with cyclophilin-D (CyPD). This complexation was required for mitochondrial permeability transition pore (mPTP) opening and subsequent programmed necrosis. Blockade of Cyp-D by siRNA-mediated depletion or pharmacological inhibitors (cyclosporin A and sanglifehrin A) significantly suppressed salinomycin-induced glioma cell necrosis. Meanwhile, p53 stable knockdown alleviated salinomycin-induced necrosis in glioma cells. Reactive oxygen species (ROS) production was required for salinomycin-induced p53 mitochondrial translocation, mPTP opening and necrosis, and anti-oxidants n-acetylcysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) inhibited p53 translocation, mPTP opening and glioma cell death. CONCLUSIONS: Thus, salinomycin mainly induces programmed necrosis in cultured glioma cells.

Treatment of recurrent malignant gliomas with 13-cis-retinoic acid naphthalene triazole.

Glioblastoma multiforme and anaplastic astrocytoma are challenges to clinical biologists at present. The patients with glioblastoma have median survival of less than 12 months, despite advances in radiotherapeutical, chemotherapeutical and conventional surgical modalities. Retinoic acids are known to effect in vitro proliferation, differentiation, and apoptosis in colon, prostate, lung, and leukemia cancers. Retinoids are known to have anti-proliferation, anti-migration, and anti-invasive activity against human malignant gliomas, suggesting that retinoids are suitable anticancer agents to inhibit progression of tumors. Recurrent malignant cerebral gliomas have been treated with ATRA and 13-cis RA. However, the side effects associated with the use of high doses of retinoic acid demand for some more potent derivative free from such effects. The present clinical trials are undertaken to investigate the clinical safety and possible efficacy of administering retinoic acid naphthalene triazole (RANT) to patients with recurrent malignant gliomas. The toxicities observed in the patients during RANT treatment were mild. These preliminary results suggest that RANT is more potent compared to RA against recurrent malignant gliomas.

Treatment of pituitary adenomas with a transsphenoidal approach.

OBJECTIVE: To evaluate the overall therapeutic effectiveness of transsphenoidal microsurgery for pituitary adenomas and explore the surgical technique, application of new technology, and postoperative follow-up. METHODS: The clinical presentation, imaging features, endocrine examination, pathological types, conditions of operation, postoperative complications, and follow-up of 4050 patients with pituitary adenomas who had undergone transsphenoidal microsurgery from December 1981 to January 2004 were analyzed retrospectively. RESULTS: During the past 6 years, total tumor resection (under microscope) has been achieved in 97.3% of the patients with Hardy Grade I adenomas, 95.2% of Hardy Grade II, 90.4% of Hardy Grade III, and 47.4% of Hardy Grade IV. The percentages of total and subtotal resection achieved extended from 87.6% before 1987 to 96.9% in 2003. CONCLUSION: With the improvement of microsurgical technique and application of novel technology, the indications for transsphenoidal microsurgery for pituitary adenomas were increasingly extended. We believe that more than 90% of pituitary adenomas could be treated by the transsphenoidal approach and totally removed through the microscope. The transnasal perpendicular plate-sphenoid sinus approach will be the dominant mode. Routine postoperative radiotherapy is not required for patients with total resection.

[The clinical evaluation of patients with pituitary adenomas undergone transsphenoidal microsurgery].

OBJECTIVE: To evaluate the overall effect of transsphenoidal microsurgery for pituitary adenomas in recent 5 years and to discuss the surgical technique, application of new technology and postoperative follow-up results. METHODS: The clinical presentation, image characteristics, endocrinal findings, pathological types, tumor removal percentage, postoperative complication and follow-up of 1 462 patients with pituitary adenomas who underwent the transsphenoidal microsurgery from 1997 to 2002 were analysed retrospectively. RESULTS: Total rate of tumor removal for the patients achieved 97.0% in the patients with Hardy I adenomas, 95.2% with Hardy II, 90.5% with Hardy III, and 47.4% with Hardy IV respectively. A significant postoperative improvement both in clinical symptoms and endocrinal parameters was achieved. The tumor recurrence rate was 0.3%. CONCLUSIONS: With the improvement of microsurgical technique and application of novel technology, the indication of transsphenoidal microsurgery for pituitary adenomas was increasingly extended. Endoscope and(/or) neuronavigation-assisted microsurgery via transsphenoidal approach should be of the first choice for the treatment of pituitary adenomas. The routine postoperative radiotherapy is not required for patients with total tumor removal.