Effect of n-3 and n-6 fatty acids on proliferation and differentiation of promyelocytic leukemic HL-60 cells

Promyelocytic leukemic HL-60 cells were incubated with different fatty acids. Arachidonic acid (AA; 20:4, n-6) and eicosapentaenoic acid (EPA; 20:5, n-3) were the most potent inhibitors of proliferation in a dose- dependent way. Retinoic acid (RA) was used as a positive control. Inhibitors of cyclooxygenase and lipoxygenase or addition of antioxidants did not influence the effect of EPA or AA on cell proliferation. Increased capacity to generate superoxide anions after phorbol ester treatment and a reduced serglycin messenger RNA level in cells treated with AA or EPA indicated that these fatty acids induced differentiation in HL-60 cells similar to that induced by RA. However, down-regulation of the c-myc mRNA level, also typical for differentiation with RA in HL-60 cells, was not observed in cells incubated with AA or EPA. Flow cytometric analyses showed that in cultures incubated with AA or EPA, the proportion of cells in the G1 phase of the cell cycle increased. Similar effects were observed with RA. By flow cytometry and light scatter analyses it could be shown that AA made 8% of the cells apoptotic and 7% necrotic. The corresponding numbers were 21% and 10% for RA-treated cells, and 19% and 32% for EPA- treated cells. The present study shows that AA and EPA reduce the proliferation rate of HL-60 cells. This is mediated by mechanisms independent of eicosanoids or lipid peroxidation products and is due to effects both on apoptosis/necrosis and cell differentiation.     

Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a preparative regimen

We have studied the use of a new preparative regimen for the treatment of patients in remission of acute myeloid leukemia (AML) with autologous bone marrow transplantation. Chemotherapy consisted of busulfan 1 mg/kg every 6 hours for 4 days (total dose, 16 mg/kg) on days -7 through -4 followed by an intravenous infusion over 6 to 10 hours of etoposide 60 mg/kg on day -3. Autologous bone marrow, treated in vitro with 100 micrograms/mL of 4-hydroperoxycyclophosphamide, was infused on day 0. We have treated 58 patients up to the age of 60 years, 32 in first remission, 21 in second or third remission, and 5 with primary refractory AML unresponsive to high-dose Ara-C, but achieving remission with aggressive salvage regimens. Of the first remission patients, there has been 1 treatment related death and 5 relapses. With median follow-up of 22 months, the actuarial relapse rate is 22% +/- 9% and disease-free survival is 76% +/- 9% at 3 years. Patients with favorable French-American-British (FAB) subtypes (M3 or M4 EO) did especially well, with no relapses seen in 15 patients observed for a median of 30 months. Actuarial relapse rate at 3 years was 48% for first remission patients with less favorable FAB subtypes. Of patients in second or third remission, there were 5 treatment related deaths and 4 relapses. With median follow-up of 22 months, the actuarial relapse rate is 25% +/- 11% and disease-free survival is 56% +/- 11% at 3 years. Four of five primary refractory patients died during treatment and 1 remains in remission with short follow-up. These preliminary data are very encouraging and, if confirmed, support the use of autologous purged bone marrow transplantation using aggressive preparative regimens as one approach to improve the outcome of adults with AML.     

Development of anatomically and lesion contrast-guided partial volume correction: new 3D formalisms and validation in phantom and clinical studies

Annals of Nuclear Medicine - The aim of the study was to correct for partial volume effect in positron emission imaging studies which is the most influential factors using three-dimensional (3D)...     

Global Forum of Cancer Surgeons: Cancer Surgery During the COVID-19 Pandemic: Impact and Lessons Learned

Annals of Surgical Oncology - The purpose of this article is to summarize the opinions of the surgical oncology leaders from the Global Forum of Cancer Surgeons (GFCS) about the global impact of...     

A randomized prospective comparison of chemotherapy to total body irradiation as initial treatment for the indolent lymphoproliferative diseases

One hundred eight consecutive patients with indolent lymphoproliferative diseases were stratified into chronic lymphocytic leukemia (CLL), stage III and IV well-differentiated lymphocytic lymphoma (WDLL), and stage III and IV follicular lymphoma (FL). Within each stratum, patients were prospectively and randomly assigned to receive chemotherapy with chlorambucil and prednisone (CP) or fractionated total body irradiation (TBI). Morbidity from both regimens was negligible. Complete response (CR) was defined as the resolution of organ enlargement and the return of blood count to normal. The CR rate for the entire CP group (n = 54) was 59% and that for the TBI group (n = 54), 52%; median survivals were 53 and 57 months respectively. In the 41 patients with CLL the CR rate for CP (n = 17) was 47% and that for TBI (n = 24), 50%; the median survival for CP was 48 months, and for TBI it was 51 months. In the 21 patients with WDLL the CR rate for CP (n = 15) was 53% and that for TBI (n = 6), 67%; the median survival for CP was 42 months and has not yet been reached for TBI. For the 46 patients with FL the CR rate for CP (n = 22) was 72% and that for TBI (n = 24), 50%; the median survival was 55 months, and for TBI it was 56 months. None of the differences in CR or survival are statistically significant (P greater than .05). In these indolent lymphoproliferative diseases, CP and TBI are equally effective forms of initial treatment irrespective of the end point being defined as CR or survival.     

Predictors of long-term survival after pancreaticoduodenectomy for peri-ampullary adenocarcinoma: A retrospective study of 5-year survivors

Background: Pancreaticoduodenectomy(PD) is the standard curative treatment for periampullary tumors. The aim of this study is to report the incidence and predictors of long-term survival( ≥ 5 years) after PD. Methods: This study included patients who underwent PD for pathologically proven periampullary adenocarcinomas. Patients were divided into 2 groups: group(I) patients who survived less than 5 years and group(II) patients who survived ≥ 5 years. Results: There were 47(20.6%) long-term survivors( ≥ 5 years) among 228 patients underwent PD for periampullary adenocarcinoma. Patients with ampullary adenocarcinoma represented 31(66.0%) of the long-term survivors. Primary analysis showed that favourable factors for long-term survival include age 60 years old, serum CEA 5 ng/mL, serum CA 19-9 37 U/mL, non-cirrhotic liver, tumor size 2 cm, site of primary tumor, postoperative pancreatic fistula, R0 resection, postoperative chemotherapy, and no recurrence. Multivariate analysis demonstrated that CA 19-9 37 U/mL [OR(95% CI) = 1.712(1.24 8–2.34 8), P = 0.001], smaller tumor size [OR(95% CI) = 1.335(1.032–1.726), P = 0.028] and R0 resection [OR(95% CI) = 3.098(2.095–4.582), P 0.001] were independent factors for survival ≥ 5 years. The prognosis was best for ampullary adenocarcinoma, for which the median survival was 54 months and 5-year survival rate was 39.0%, and the poorest was pancreatic head adenocarcinoma, for which the median survival was 27 months and 5-year survival rate was 7%. Conclusions: The majority of long-term survivors after PD for periampullary adenocarcinoma are patients with ampullary tumor. CA 19-9 37 U/mL, smaller tumor size, and R0 resection were found to be independent factors for long-term survival ≥ 5 years.     

Determinants of wait time for infant inguinal hernia repair in a Canadian children’s hospital

Background

Longer wait time for infant inguinal hernia (IH) repair is associated with higher complication rates. We wished to determine if socioeconomic and demographic factors influence wait times for IH repair.

Methods

Children < 2 years old with IH at a Canadian children’s hospital were retrospectively reviewed. Days from diagnosis to surgical consultation (W1) and from consultation to repair (W2) were collected along with demographic, medical, and socioeconomic data. Linear regression analysis was performed.

Results

A total of 131 patients were appropriate for analysis (82.4% male). Median distance to hospital was 27.5 km (IQR = 10.5–50.4) and median income was $34,477 (IQR = 30,127–41,986). Median W1, W2, and Wtotal (W1 + W2) were 24 (IQR = 8–48), 43 (IQR = 21–69) and 79 (IQR = 38–112) days, respectively. Wait times were shorter in infants who were male (p = 0.044), symptomatic (p < 0.001), diagnosed in the ED (p < 0.001), or had an incarcerated hernia (p = 0.006). They were longer for premature infants (p = 0.009) and those with significant comorbidities (p = 0.018). Neither income (p = 0.328) nor distance from hospital (p = 0.292) was associated with longer wait times.

Conclusion

Wait times for IH repair were appropriately influenced by medical risk factors. Income and distance to hospital did not appear to influence wait times. A population-based study is needed to determine if these findings reflect a general trend within the Canadian health care system.     

Cognitive decline and depressive symptoms: early non-motor presentations of parkinsonism among Egyptian Gaucher patients

neurogenetics - Evidence about the link between glucocerebrosidase (GCase) and parkinsonism is growing. Parkinsonism was described in adult type 1 Gaucher disease (GD); few case reports described...