Implications for immunotherapy of tumor-mediated T-cell apoptosis associated with loss of the tumor suppressor PTEN in glioblastoma

The ability of glioma cells to escape the immune system remains a significant barrier to successful immunotherapy. Here we demonstrate that loss of the PTEN tumor suppressor gene, with associated activation of the PI3K/Akt/mTOR pathway, leads to a human glioma phenotype that induces autologous T-cell apoptosis upon contact. The PTEN status of pathologically confirmed glioblastoma specimens was defined, and primary cultures established after surgical resection of tumor from 26 patients. Autologous T-cells were isolated from these patients, and after T-cell activation was induced, these cells were co-cultured with matched autologous glioma cells, either alone, or after treatment with one of three inhibitors of the PI3K/Akt/mTOR pathway. When co-cultured with autologous T-cells, PTEN wild-type tumor cells induced apoptosis in a minimal number of activated T-cells (6–12% of T-cells), whereas tumors with PTEN loss induced much more profound levels of T-cell apoptosis (42–56% of T-cells). Prior treatment of PTEN-deficient tumor cells with specific inhibitors of the PI3K/Akt/mTOR pathway diminished T-cell apoptosis to levels seen after co-culture with wild-type PTEN tumor cells, suggesting that PTEN loss confers this immunoresistant phenotype through the PI3K/Akt/mTOR pathway. These results suggest that PTEN-deficient glioblastoma patients are suboptimal candidates for immunotherapy. In addition, our results raise the possibility of combining T-cell based immunotherapy protocols with clinical inhibitors of the PI3K/Akt/mTOR pathway.     

The effect of n-3 fatty acids on bone biomarkers in Iranian postmenopausal osteoporotic women: a randomized clinical trial

Recently, n-3 fatty acids are in the center of attention for their potent anti-inflammatory effects. Osteoporosis as a chronic senile disease is associated with inflammation, and the role of inflammatory mediators has been demonstrated in recent years. The beneficial effects of n-3 fatty acids on bone were proven in many animal studies, while to date, no conclusive data is available in human. The aim of this study was to evaluate the impact of n-3 fatty acids on bone biomarkers in osteoporotic postmenopausal women. Twenty-five osteoporotic postmenopausal women were recruited in the study and randomized in treatment and control groups. The patients received 900 mg n-3 fatty acid capsules or placebo per day for 6 months. Serum levels of osteocalcin, bone alkaline phosphatase (BALP), calcium, vitamin D, and parathormone and urine concentration of pyridinoline (Pyd) were measured at baseline, second month, and sixth month in both groups. In the treatment group, compared with baseline, at the second month, osteocalcin increased slightly; thereafter, it showed decrement trend until the end of the study. In the control group, it decreased all over the study. None of these changes was significant. BALP showed nonsignificant decrease from baseline over the time in both groups. Urine level of Pyd decreased significantly (P < 0.05) in the treatment group, while no significant change was seen in the control group. Serum calcium and vitamin D increased in both groups; however, changes were not significant. No significant changes were seen in calcium clearance and parathormone. In conclusion, n-3 fatty acids can decrease bone resorption; however, it could not affect bone formation significantly after 6 months treatment. Further investigations are recommended.     

A systematic review of intracranial chondrosarcoma and survival

Most data regarding survival in patients with chondrosarcoma are limited to case studies and small series performed at single institutions. A systematic review was performed to study the relationship between potential prognostic factors and survival. The survival rates were analyzed according to modality of treatment, treatment history, histological subtype, and histological grade. A total of 560 patients with intracranial chondrosarcoma were analyzed. Median follow-up time was 60 months. The 5-year mortality among all patients was 11.5% with median survival of 24 months. Mortality at 5 years was significantly greater for patients with tumors of higher grade, or of the mesenchymal subtype, or who had received surgical resection alone. The results of our systematic review provide useful data in predicting survival among intracranial chondrosarcoma patients.     

Adjustment process in Iranian women with breast cancer

Breast cancer is a devastating event for a woman. Physical changes and psychological problems, treatment to improve the patient's condition, and increased survival rates compared with other cancers manifest the importance of quality of life in these patients. This quality of life is affected by how the patients adjust to their situation. Hence, to understand adjustment to breast cancer, this research aimed to investigate the experience from the patients' perspective and how they interact with others and interpret their experiences in adjusting to the disease. A qualitative research approach based on grounded theory was used. The data were the result of 45 interviews with patients in different phases of their illness trajectory during 1 year, 6 interviews with families, and 10 observation sessions. The main categories that emerged were perceived threat to live, religious aspects, supportive dimensions, will to recover, increase in endurance, barriers to efforts leading to health, living with the disease with tolerance, and inhibitors and facilitators of tolerance. These main categories were understood as passages to reach evolutionary peaceful coexistence. Adjustment to breast cancer has positive evolutional process, and its direction is toward better adjustment. By positive mental reconstruction, the patients feel that they can live with their disease.     

Hiccup and neurosurgeons: a report of 4 rare dorsal medullary compressive pathologies and review of the literature

OBJECTIVE: The aim of this study was to present 4 rare cases of medullary compressive lesions presenting with IH, to discuss the indications for neurosurgical decompression in such cases, and to review the possible etiologies of IH briefly. METHODS: The reported cases include (1) a 19-year-old adolescent boy and a 21-year-old man with Chiari I malformation and cervical syrinx compressing or tightening the cervico-medullary junction; (2) a 35-year-old man with ependymoma extending from the lower half of the fourth ventricle to C1/C2 junction and compressing this part of the medulla; and (3) a 16-year-old adolescent boy who was referred to the emergency department in severe distress because of IH, occurring as a result of a distal PICA aneurysm located on the floor of the lower triangle of the fourth ventricle. RESULTS: Surgical decompression in all the cases was successful in withholding the hiccups. CONCLUSION: The dorsal medullary area is not an unusual location for genesis of hiccup. When encountering a case of IH, appropriate CNS imaging studies should be included in the evaluation protocol.     

Occipital ganglioglioma in an older adult

Gangliogliomas are rare benign tumors of the central nervous system that typically involve the temporal lobe in younger patients. We present a 63-year-old man with an unusual occipital ganglioma with new seizures resolving after resection. A search of the literature revealed only three reports of occipital ganglioma in adults over 30 years old. Therefore, ganglioglioma of the occipital lobe in older patients is rare, but is a diagnostic consideration.     

Conventional screen/film vs reduced exposure photostimulable phosphor plate imaging in lower extremity venography: an ROC analysis

Half-exposure phosphor plates used in venography substantially reduce the total X-ray exposure to a patient while increasing the chance that all images will be of excellent diagnostic quality. Simultaneous half-exposure phosphor plate and full-exposure conventional screen/film venograms were obtained of 35 patients and compared by using receiver operating characteristic (ROC) analysis. The area under the ROC curve ranged from 0.67 to 0.78 for conventional films and 0.68 to 0.91 for phosphor plates. Group performances on conventional films vs phosphor plates were not statistically different. No statistically significant difference in individual performance with the two techniques was seen in seven of the eight interpreters at the 95% confidence level. The eighth interpreter performed significantly better with phosphor plates than with conventional films. Interpreters with and without specific experience in phosphor plate venography were grouped separately, and performance of the two groups was compared in each technique. No difference in performance was found between the groups when interpreting conventional venograms, but, when interpreting phosphor plate venograms, the group with specific experience performed significantly better than they had with conventional venograms, and significantly better than the other group did at interpreting either conventional or phosphor plate venograms. We conclude that phosphor plate venograms made at a 50% reduction in X-ray exposure are equal to, and may surpass, conventional screen/film venograms for diagnosing acute venous thrombosis of the calf and thigh. We recommend expanding the indications for phosphor plate radiography to include contrast venography of the lower extremities.