Detection of M2 macrophages and colony-stimulating factor 1 expression in serous and mucinous ovarian epithelial tumors

Tumor-associated macrophages (TAM) are known to possess the immunosuppressive M2 macrophage phenotype. They contribute to tumor growth, invasion, and metastasis by producing various mediators. Macrophages, especially M2 polarized macrophages, preferentially express CD163 and CD204, but few studies have investigated macrophage phenotypes in human ovarian tumors. The purpose of the present study was therefore to present results on macrophage differentiation in human ovarian serous and mucinous epithelial tumors. The method focused on immunostaining of paraffin-embedded tumor samples. Almost all macrophages infiltrating tumor tissues expressed CD163 and CD204, indicating the phenotypic shift toward M2 macrophage. The numbers of CD68-positive macrophages as well as of CD163- and CD204-positive macrophages in borderline and malignant tumors were significantly higher than in benign tumors. They correlated well with histological gradient of malignancy. Macrophage colony-stimulating factor (also known as colony-stimulating factor; CSF-1), which is one of the cytokines considered to induce TAM to polarize toward an M2 phenotype, was then evaluated. CSF-1 expression in malignant tumor cells was significantly higher than that in benign tumor cells and correlated with histological malignancy. These results suggest that CSF-1 derived from tumor tissues induces macrophages to shift toward the M2 phenotype, which is considered to promote tumor growth.     

Seven new dammarane triterpenes from the floral spikes of Betula platyphylla var. japonica

Seven new dammarane-type triterpenoids, including two 20(S)-hydroxy-25-methoxy-dammar-23-enes (1 and 2), two 20(S),24(R)-epoxydammaranes (3 and 4), a cabralealactone (5), and two 20(S),25-epoxydammaranes (6 and 7), together with seven known triterpenes (8–14), were isolated from the floral spikes of Betula platyphylla var. japonica. The structures for all compounds were elucidated by the analyses of extensive spectroscopic data, as well as chemical examinations.     

Surgical treatment of intramedullary spinal cord tumors: prognosis and complications

STUDY DESIGN: Retrospective case series. OBJECTIVE: To evaluate our recent treatment strategy for intramedullary spinal cord tumors. SETTING: Department of Orthopaedic Surgery, Keio University, Japan. METHODS: We reviewed 68 cases of intramedullary tumors (ependymoma, 33; astrocytoma, 23; hemangioblastoma, 12), treated surgically between 1994 and 2003. There were 42 males and 26 females whose mean age at the time of surgery was 43 years. The mean follow-up period was 6.2 years. The tumor malignancy grade according to the WHO classification was astrocytoma grade I, 3; grade II, 8 (low-grade: 11 cases); grade III, 10; grade IV, 2 (high-grade: 12 cases). All ependymomas were grade II. Three of the 12 hemangioblastomas were associated with von Hippel-Lindau disease. RESULTS: Total excision was achieved in 90% of the ependymomas and functional improvement was obtained when the preoperative neurological deficit was mild. Approximately 50% of low-grade astrocytomas could be totally excised with favorable survival outcomes, suggesting that total excision should be attempted for low-grade astrocytomas. However, total excision of high-grade tumors was difficult and the functional outcomes were poor. Cordotomy should be considered in patients with a thoracic high-grade astrocytoma. Total resection was possible in 92% of hemangioblastoma, and the functional outcomes were good, however, more attention should be paid for tumors with feeding arteries on the ventral side and for those associated with von Hippel-Lindau disease. CONCLUSIONS: Predictors of good surgical outcome for intramedullary spinal cord tumors were histological grades of the tumors, surgical margins, and neurological status of the patient before surgery.     

Effect of unilateral pulmonary vagotomy on respiratory control in man

We studied the breathing pattern and pulmonary function at rest, and ventilatory responses to progressive hypoxia and hypercapnia in 7 awake patients who had undergone esophageal-carcinoma resection with sectioning of the right pulmonary vagal branch by lymphadenectomy. Twelve control patients, who had received the same surgery without vagotomy, were also studied by the same protocol. Two months after the operation, both patient groups demonstrated substantial depressions in FVC and FEV1.0, and slight augmentations in breathing frequency, minute ventilation, and occlusion pressure at 0.2s (P0.2) at rest. In the vagotomized group, the occlusion pressure responses to hypercapnia (delta P0.2/delta PaCO2) and hypoxia (delta P0.2/delta SaO2) in terms of response curve slope increased from 1.3 +/- 1.2 to 1.9 +/- 1.1 cm H2O/Torr and from 0.29 +/- 0.19 to 0.88 +/- 0.53 cm H2O/% (p less than 0.05), respectively. Contrary to the vagotomized patients, the nonvagotomized control group exhibited no significant changes in ventilatory chemosensitivities. Furthermore, when comparing the control and vagotomized groups, postoperative ventilatory chemosensitivity responses in terms of both hypercapnic and hypoxic occlusion pressure responses were significantly higher in the latter. We suggest that (1) due to the development of the substantial mechanical limitation in pulmonary functions, the Hering-Breuer inflation reflex became activated after surgery, and (2) a diminished Hering-Breuer reflex effect to inhibit the respiratory centers by unilateral vagotomy may have resulted in augmented ventilatory chemosensitivities.     

A novel apoptosis-inducing monoclonal antibody (anti-LHK) against a cell surface antigen on colon cancer cells

Background Apoptosis is a crucial element in the behavior of mammalian cells in many different situations. We here report the establishment of a novel monoclonal antibody (anti-LHK mAb) that has apoptosis-inducing activity against colon cancer Colo205 cells. Methods The mechanism of anti-LHK mAb-induced cell death was assessed by microscopic morphology, Annexin V/Hoechst 33528 staining, and detection of DNA fragmentation. The molecular weight of LHK antigen was determined by Western blotting. Growth inhibition of Colo205 cells induced by anti-LHK mAb was determined by in vitro and in vivo studies. Results Anti-LHK reacted with a 70-kDa antigen and completely blocked the proliferation of Colo205 cells bearing LHK in vitro in a manner characteristic of apoptosis. Strikingly, anti-LHK mAb suppressed tumor growth in a murine peritoneal dissemination model. Conclusions LHK antigen, which is restricted to epithelial cells, may be a novel death receptor that plays a critical role in controlling the growth, invasion, and metastasis of human colon cancer cells.     

Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative acute kidney injury

The aim of the present study was to evaluate the usefulness of a closed-loop system (STG-55; Nikkiso, Tokyo, Japan), a type of artificial endocrine pancreas for the continuous monitoring and control of intraoperative blood glucose, for preventing postoperative acute kidney injury (AKI) in patients undergoing hepatectomy. Thirty-eight patients were enrolled in this study. Glucose concentrations were controlled with either a manual injection of insulin based on a commonly used sliding scale (manual insulin group, n = 19) or the programmed infusion of insulin determined by the control algorithm of the artificial endocrine pancreas (programmed insulin group, n = 19). After the induction of anesthesia, a 20-G intravenous catheter was inserted into the peripheral forearm vein of patients in the programmed insulin group and connected to an artificial endocrine pancreas (STG-55). The target range for glucose concentrations was set to 100–150 mg/dL. The mean serum creatinine concentrations of preoperative, postoperative 24 and 48 h were 0.72, 0.78, and 0.79 mg/dL in the programmed insulin group, and 0.81, 0.95, and 1.03 mg/dL in the manual insulin group, respectively. Elevations in serum creatinine concentrations postoperative 48 h were significantly suppressed in the programmed insulin group. The STG-55 closed-loop system was effective for maintaining strict blood glucose control during hepatectomy with minimal variability in blood glucose concentrations and for suppressing elevations in serum creatinine concentrations. Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative AKI.