Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis.

Optic neuritis is an acute inflammatory demyelinating disorder of the optic nerve (ON) and is an initial symptom of multiple sclerosis (MS). Optic neuritis is characterized by ON degeneration and retinal ganglion cell (RGC) loss that contributes to permanent visual disability and lacks a reliable treatment. Here, we used the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, a well-established model also for optic neuritis. In this model, C57BL6 mice, intraperitoneally injected with a fragment of the myelin oligodendrocyte glycoprotein (MOG), were found to develop inflammation, Müller cell gliosis, and infiltration of macrophages with increased production of oncomodulin (OCM), a calcium binding protein that acts as an atypical trophic factor for neurons enabling RGC axon regeneration. Immunolabeling of retinal whole mounts with a Brn3a antibody demonstrated drastic RGC loss. Dietary supplementation with Neuro-FAG (nFAG®), a balanced mixture of fatty acids (FAs), counteracted inflammatory and gliotic processes in the retina. In contrast, infiltration of macrophages and their production of OCM remained at elevated levels thus eventually preserving OCM trophic activity. In addition, the diet supplement with nFAG exerted a neuroprotective effect preventing MOG-induced RGC death. In conclusion, these data suggest that the balanced mixture of FAs may represent a useful form of diet supplementation to limit inflammatory events and death of RGCs associated to optic neuritis. This would occur without affecting macrophage infiltration and the release of OCM thus favoring the maintenance of OCM neuroprotective role.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for treatment of ovarian cancer.

Hyperthermic intraperitoneal chemotherapy (HIPEC), a strategy combining maximal cytoreductive surgery and maximal regional chemotherapy, has been applied to treat ovarian cancer resulting in long-term survival rates in selected patients. However, the status of HIPEC in ovarian cancer remains an experimental procedure, given the many variables among the data and trials reviewed, to enable us to derive strong conclusions about its role from this overview. In this review we discuss treatment with HIPEC in patients with ovarian cancer and future prospective of its use in clinical setting. HIPEC is an effective tool in the treatment of selected patients with peritoneal carcinomatosis from ovarian cancer. Unfortunately, due to the lack of randomised trials, the evidence of HIPEC is very limited. Future randomised studies are awaited to define the role and clinical impact of HIPEC in ovarian cancer.

Safety and potential benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal carcinomatosis from primary or recurrent ovarian cancer.

OBJECTIVES: To analyze the outcomes of cytoreductive surgery and HIPEC in patients with peritoneal carcinomatosis from ovarian cancer. METHODS: Fifty-three patients with peritoneal carcinomatosis from primary (45 cases) and recurrent (8 cases) ovarian cancer were previously treated by systemic chemotherapy with platinum and taxanes and then submitted to surgical cytoreduction and HIPEC (cisplatin and mitomycin-C) with a closed abdomen technique. The median follow-up period was 27 months (range: 3-107). RESULTS: At the end of operation a complete cytoreduction (CCR-0) was obtained in 37 patients (70%). Major morbidity occurred in 12 patients (23%); reoperation was necessary in 2 patients (4%), and no postoperative mortality was observed. Overall 5-year survival probability was 55%; it was 71% in CCR-0, 44% in CCR-1, and none in patients with CCR-2 or CCR-3 residual tumor (log-rank test: P = 0.017). The cumulative risk of recurrence in 37 CCR-0 cases was 54% at 5 years from operation. CONCLUSIONS: The results of our study indicate the feasibility and the potential benefit of a protocol including systemic chemotherapy, surgical cytoreduction and HIPEC in patients with peritoneal carcinomatosis from ovarian cancer. A phase III trial to compare this approach with conventional treatment is needed.

Neurotoxicity of FOLFOX-4 as adjuvant treatment for patients with colon and gastric cancer: a randomized study of two different schedules of oxaliplatin.

PURPOSE: The dose limiting toxicity of oxaliplatin (l-HOP) is neurotoxicity, which is characterized by an acute neuropathy and a clinically distinct chronic neuropathy. This randomized study evaluated if prolonged l-HOP infusion over the conventional l-HOP schedule was useful in reducing acute and possibly chronic l-HOP induced neurotoxicity in colon and gastric cancer patients receiving l-HOP-based regimen as adjuvant chemotherapy. METHODS: Sixty-four patients were randomly assigned to group A (26 colon and 6 gastric cancer) and to group B (23 colon and 9 gastric cancer). Chemotherapy in both groups consisted of l-HOP 85 mg/m(2) i.v. only on day 1, with leucovorin 100 mg/m(2) i.v. as a 2-h infusion followed by bolus 5-fluorouracil (5-FU) 400 mg/m(2)/day and a 22-h infusion of 5-FU 600 mg/m(2)/day, repeated for two consecutive days every 2 weeks for a maximum of 12 cycles. Patients in group A received l-HOP as a continuous 6-h i.v. infusion, and patients in group B received l-HOP as the conventional 2-h i.v. infusion. RESULTS: The percentage of patients presenting with grade >/=2 neurotoxicity was statistically lower in group A than in group B (28.1% vs. 59.3%: P = 0.02). There was a statistically lower percentage of cycles with grade >/=2 neurotoxicity in group A (6.1%) than in group B (18.5%) (P < 0.001). CONCLUSIONS: This study suggests that l-HOP as a continuous 6-h infusion is useful in preventing and reducing acute l-HOP induced neurotoxicity in patients with colon and gastric cancer receiving FOLFOX-4 regimen as adjuvant treatment.

Weekly high-dose calcitriol and docetaxel in patients with metastatic hormone-refractory prostate cancer previously exposed to docetaxel.

OBJECTIVE: To evaluate the activity and tolerability of weekly high-dose calcitriol and docetaxel in patients with metastatic hormone-refractory prostate cancer (HRPC) previously exposed to docetaxel, as patients who progress after docetaxel treatment might be considered for second-line chemotherapy, but with no standard salvage therapy available we hypothesised that high-dose calcitriol might restore sensitivity to chemotherapy. PATIENTS AND METHODS: The study comprised 26 patients who had progressed after first-line treatment with docetaxel-based chemotherapy had failed. Treatment cycles consisted of calcitriol (32 microg orally as 0.5 microg tablets) on day 1 and docetaxel (30 mg/m(2) intravenous) on day 2, administered for six consecutive weeks followed by a 2-week rest interval for a maximum of 24 cycles. RESULTS: There was a response in prostate-specific antigen (PSA) level in eight patients (31%); seven (27%) had a stable PSA level for >/= 12 weeks. The median time to PSA progression was 4.2 months and the median survival was 9.3 months. The regimen was generally well tolerated; there was grade 2 hypercalcaemia, probably related to calcitriol, in one patient after six treatment cycles. CONCLUSION: Weekly high-dose calcitriol and docetaxel seems to be an effective and well-tolerated treatment option for patients with metastatic HRPC previously exposed to docetaxel-based chemotherapy.

Folinic acid, 5-fluorouracil and etoposide after curative resection for gastric cancer.

BACKGROUND/AIMS: The aim of this study was to evaluate the survival benefit of adjuvant chemotherapy with etoposide, leucovorin and 5-fluorouracil (ELF) in gastric cancer patients undergoing previous surgery with a curative intent. METHODOLOGY: The clinical outcome of 49 patients with resected gastric cancer treated with adjuvant chemotherapy was compared with that of 85 surgically treated historical controls who did not receive any adjuvant treatment. The chemotherapy regimen consisted of six cycles of daily 1-hour intravenous infusions of folinic acid 100 mg/m2 and 5-FU 400 mg/ m2, and a 2-hour infusion of etoposide 100 mg/m2, for three days every 28 days. RESULTS: The 5-year relapse-free survival was 32% in the adjuvant arm and 27% in the control arm (p = 0.6). At the last follow-up, there were 32 deaths in the adjuvant arm and 60 in the control arm. The median duration of survival was respectively 23 and 19 months, and the 5-year survival rates were 34% and 29% (p = 0.4). The chemotherapy was well tolerated. CONCLUSIONS: Our data suggest that ELF adjuvant treatment is a safe and well tolerable combination chemotherapy in patients with resected gastric cancer, but it does not seem to improve prognosis in comparison with historical controls.