A Hybrid Glioma Tumor Cell Lysate Immunotherapy Vaccine Demonstrates Good Clinical Efficacy in the Rat Model.

BACKGROUND: Conventional immunotherapy for glioma is not only expensive but also demonstrates less-than-desired clinical efficacy. In this study, we evaluated the immunotherapeutic efficacy of a tumor cell lysate-based hybrid glioma vaccine developed using a molecular-based approach. METHODS: First, the ability of the autologous (9L-cell lysate) and allogeneic (C6-cell lysate) vaccines against glioma, individually and in combination, to activate Fischer344 rat dendritic cells (DCs) was determined. Next, the activated DCs were co-cultured with T lymphocytes and screened for the optimal DC-to-T-cell ratio. The in vitro efficacy of the DC/T-cell vaccine formulations subjected to different immunogen treatments and co-cultured with glioma cells was evaluated based on glioma cell viability and monocyte chemoattractant protein (MCP)-2 and interferon (IFN)-γ secretion. Subsequently, the efficacy of the 9L + C6 hybrid vaccine was evaluated in 32 glioma rat models, randomly allocated to the following five treatment groups: blank control, tumor, vaccine treatment, thymosin treatment, and vaccine + thymosin treatment (combined treatment). Changes in survival duration, intracranial tumor volume, peripheral blood immune-cell (CD4+ T, CD8+ T, and natural killer [NK] cell) count, and serum cytokine (interleukin [IL]-2, IL-10) levels were assessed in these groups. RESULTS: The hybrid vaccine demonstrated the highest glioma cell apoptosis and the lowest cell viability and promoted MCP-2 and IFN-γ secretion in vitro. The vaccine treatment and combined treatment groups demonstrated longer survival duration, lower intracranial tumor volume, and higher immune cell glioma tissue infiltration and IL-2 secretion than the untreated tumor group, indicating the vaccine's good in vivo efficacy. Thymosin treatment had minimal effect in enhancing anti-glioma immunity. CONCLUSION: We demonstrated the feasibility of combining autologous and allogeneic tumor cell lysates to stimulate specific host cell immune response against glioma cells. The good clinical efficacy of our developed glioma hybrid vaccine in rat models suggests its potential clinical application.

[The Role of Cancer-associated Fibroblasts in Invasive Behavior of Pituitary Adenoma].

OBJECTIVE: To determine the role of cancer associated fibroblasts (CAFs) in the invasive behavior of pituitary adenoma. METHODS: Pituitary adenoma tissues were divided into invasive group (IPA) and non-invasive group (nIPA) according to pre-operative MRI and observations during surgery. Those tissues were cultured and CAFs were identified through a smooth muscle actin (α-SMA). The migratory and invasive ability of CAFs was tested with transwell migration and invasion assay. The expressions of α-SMA and matrix metalloproteinase (MMP)-9 from CAFs were determined by immunocytochemistry and Western blot. RESULTS: All cultured CAFs expressed α-SMA. No significant difference in migratory ability of CAFs was found between the IPA and nIPA tissues; however, CAFs from the IPA tissues had stronger invasive ability than those from the nIPA tissues (P= 0. 010). Higher levels of MMP-9 expression were found in group IPA as compared with nIPA (P=0. 025). No significant difference in the expression of α-SMA was found between the two groups. CONCLUSION: CAFs may promote invasive behavior by secreting more MMP-9, which may play a part in the invasive behavior of pituitary adenomas.

[Postoperative management of patients with sellar tumors through monitoring urine volume and urine electrolytes].

OBJECTIVE: To determine the value of urine volume and urine electrolytes in postoperative management of patients with sellar tumors. METHODS: Medical records of 103 patients with sellar tumors in the West China Hospital from January 2009 to December 2009 were retrospectively reviewed. The patients were managed either based on blood electrolytes (Group A, n = 56) or based on urine volume and urine electrolytes (Group B, n = 47). The incidence of balance disturbance of water and electrolytes was compared between the two groups. RESULTS: The levels of blood electrolytes were normal in both groups 3 days after operations despite significant loss of electrolytes through urine. Balance disturbance of water and electrolytes was revealed 4-7 days after operations. Group B had a lower incidence of balance disturbance of water and electrolytes (17.02%, 8/47) compared with Group A (73.21%, 41/56, P < 0.05). No gender difference in the incidence of balance disturbance of water and electrolytes was found. Higher incidence of balance disturbance of water and electrolytes was found in craniopharyngioma (P < 0.05, vs. pituitary adenoma) and in the patients undergoing craniotomy (P < 0.05, vs. transsphenoidal approach) in Group A, but not in Group B. CONCLUSION: Better management of balance disturbance of water and electrolytes can be achieved for patients with sellar tumors through monitoring urine than through blood. It can also simplify the postoperative management of patients with sellar tumors.

[Repair and reconstruction of diaphragmatic defect during transcranial pituitary adenoma surgery].

OBJECTIVE: To investigate the application value of titanium-clip and artificial menigeal in the sella diaphragm repair and reconstruction during transcranial pituitary adenoma surgery. METHODS: Thirty eight patients undergoing transcranial pituitary adenoma surgery received sella diaphragmatic defect repair and reconstruction after the removal of tumor, intraoperative diaphragmatic defect was classified as three grades, titanium-clip, artificial menigeal and EC glue were used for the sella diaphragmatic repair and reconstruction. The short-term and long-term complications were compared with those in the control group which contains 74 patients without diaphragmatic reconstruction. RESULTS: As 14 to 46 months' follow-up in the diaphragmatic reconstruction group, there were no leakage of cerebrospinal fluid(CSF), infections, empty sella syndrome (ESS), optic nerve damage, and any other severe complications was found. Only one inter-sella hemorrhage without optic nerve damage was found 3 hours after surgery by CT scan. In the group without diaphragmatic reconstruction, more secondary empty sella, cerebrospinal fluid rhinorrhea and intra-cranial infection were found after the following transsphenoidal surgery (P < 0.05), there was one case underwent the 2nd time transcranial surgery 1 hours later due to severe inter-sella hemorrhage resulting in vision damage and conscious disturbance. There was no significant difference in pituitary function and vision improvement between the two groups as the occurrence of diabetes insipidus (P > 0.05). CONCLUSION: It is important to repair the sellae diaphragm defect during transcranial pituitary adenoma surgery, which could reduce short-term and long-term complication.