Expression of the costimulatory molecule B7-H3 is associated with prolonged survival in human pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Costimulatory signaling has been implicated as a potential regulator of antitumor immunity in various human cancers. In contrast to the negative prognostic value of aberrant B7-H1 expression by pancreatic cancer cells, the role of B7-H3 is still unknown. Therefore, we investigated the expression pattern and clinical significance of B7-H3 expression in human pancreatic cancer.</p> <p>Methods</p> <p>B7-H3 expression was evaluated by immunohistochemistry in 68 patients with pancreatic cancer who underwent surgical tumor resection. Expression data was correlated with clinicopathologic features and with the number of tumor-infiltrating T cells.</p> <p>Results</p> <p>B7-H3 expression was significantly upregulated in pancreatic cancer compared to normal pancreas (p < 0.05). In 60 of 68 examined tumors B7-H3 protein was detectable in pancreatic cancer cells. Patients with high tumor B7-H3 levels had a significantly better postoperative prognosis than patients with low tumor B7-H3 levels (p = 0.0067). Furthermore, tumor B7-H3 expression significantly correlated with the number of tumor-infiltrating CD8+ T cells (p = 0.018).</p> <p>Conclusion</p> <p>We demonstrate for the first time that B7-H3 is abundantly expressed in pancreatic cancer and that tumor-associated B7-H3 expression significantly correlates with prolonged postoperative survival. Our findings suggest that B7-H3 might play an important role as a potential stimulator of antitumor immune response in pancreatic cancer.</p

Glucosylceramide synthase inhibitors induce ceramide accumulation and sensitize H3K27 mutant diffuse midline glioma to irradiation

H3K27M mutant (mut) diffuse midline glioma (DMG) is a lethal cancer with no effective cure. The glycosphingolipids (GSL) metabolism is altered in these tumors and could be exploited to develop new therapies. We tested the effect of the glucosylceramide synthase inhibitors (GSI) miglustat and eliglustat on cell proliferation, alone or in combination with temozolomide or ionizing radiation. Miglustat was included in the therapy protocol of two pediatric patients. The effect of H3.3K27 trimethylation on GSL composition was analyzed in ependymoma. GSI reduced the expression of the ganglioside GD2 in a concentration and time-dependent manner and increased the expression of ceramide, ceramide 1-phosphate, sphingosine, and sphingomyelin but not of sphingosine 1-phosphate. Miglustat significantly increased the efficacy of irradiation. Treatment with miglustat according to dose recommendations for patients with Niemann–Pick disease was well tolerated with manageable toxicities. One patient showed a mixed response. In ependymoma, a high concentration of GD2 was found only in the presence of the loss of H3.3K27 trimethylation. In conclusion, treatment with miglustat and, in general, targeting GSL metabolism may offer a new therapeutic opportunity and can be administered in close proximity to radiation therapy. Alterations in H3K27 could be useful to identify patients with a deregulated GSL metabolism

ICAR: endoscopic skull‐base surgery

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Expanding the borders: the evolution of neurosurgical approaches

In this article the authors discuss the development of neurosurgical approaches and the advances in science and technology that influenced this development throughout history. They provide a broad overview of this interesting topic from the first attempts of trephination by ancient cultures to the work of the pioneers of neurosurgery and the introduction of microsurgery

Results and risk factors for recurrence following endoscopic endonasal transsphenoidal surgery for pituitary adenoma

BACKGROUND: Endoscopic endonasal (EE) transsphenoidal surgery is an important surgical approach to the treatment of sellar pathology, particularly for pituitary adenomas. Risk factors for the radiographic recurrence of pituitary adenomas resected using a purely endoscopic approach have not been established. This study investigates outcomes and identifies risk factors for recurrence following EE transsphenoidal surgery for pituitary adenoma. METHODS: We performed a retrospective review of 64 patients with pituitary adenomas undergoing EE surgery by a single, right-handed surgeon preferentially operating through the right nares. Post-operative MRI studies were utilized to monitor for residual disease or disease recurrence. RESULTS: Residual tumor was found in 31.2% of patients. Over a median follow-up period of 23.1 months (range 4-62.5), 4 (20%) of these patients showed recurrence. Two patients with inconclusive post-operative imaging had subsequent imaging consistent with recurrence, making the total recurrence in our series 9.4%. While no statistically significant effects of gender, age or history of previous treatment were seen, amenorrhea on presentation and maximum tumor diameter \u3e10 mm were significant risk factors for radiographic recurrence (p = 0.044 and 0.005, respectively). No predominant side of residual tissue was identified in these tumors operated through the right nares. CONCLUSIONS: Only 20% of patients with residual tumor developed recurrent disease over a median follow up of 23.1 months. This recurrence rate may be an important consideration in cases where gross total resection is not feasible. Preferentially operating from the right does not seem to influence the location of residual tumor