Glioblastoma in the elderly

The incidence of malignant gliomas in the aging population of industrialized countries is increasing. This observation justifies an important ongoing clinical research effort specifically dedicated to this population. The first results of prospective studies have showed the interest of radiotherapy and chemotherapy with temozolomide. The effect of combined concomitant and adjuvant chemotherapy with radiotherapy is currently being evaluated in a phase III study. The likely beneficial effect of surgical resection needs to be formally demonstrated in this fragile population. Initial functional status, quality of life and concomitant systemic pathologies are important factors to tailor the treatment according to patients status.     

Lactate and liver function tests after living donor right hepatectomy: a comparison of solutions with and without lactate

Background: Hyperlactatemia can predict the prognosis of patients undergoing liver resection. The effects of lactated Ringer's solution on liver function have not been evaluated in patients undergoing major liver resection. We therefore compared the effects of two different crystalloid solutions, with and without lactate, on liver function test data and serum lactate level in living donors undergoing right hepatectomy. Methods: A total of 104 donors undergoing right hepatectomy for liver transplantation were randomly allocated to receive lactated Ringer's (LR) solution (n=52) or Plasmalyte (n=52). Anesthetic and fluid management were standardized. Acid–base status, lactate concentration, and liver function tests were analyzed at predetermined time points during the first 5 post‐operative days. Results: The lactate concentrations were significantly higher in the LR group than in the Plasmalyte group 1 h after hepatectomy [4.2 (3.2–5.7) vs. 3.3 (2.6–4.6) mmol/l; P=0.005, median (interquartile ranges)]. In addition, the nadir concentration of albumin was significantly lower and the peak total bilirubin concentration and prothrombin time were significantly higher in the LR group compared with the Plasmalyte group. However, these changes in the LR group subsided within the first or second post‐operative days, without apparent complications or prolongation of hospital stay. Post‐operative peak concentrations of lactate were not correlated with nadir albumin concentration, peak bilirubin, or peak prothrombin time, in either group. Conclusion: This prospective randomized study showed that non‐lactate‐containing crystalloid solution may have important advantages over LR solution, concerning lactate and liver profiles, in living donors undergoing right hepatectomy.     

Performance status is the most powerful risk factor for early death among patients with advanced soft tissue sarcoma: the European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (STBSG) and French Sarcoma Group (FSG) study

Background:

We investigated prognostic factors (PFs) for 90-day mortality in a large cohort of advanced/metastatic soft tissue sarcoma (STS) patients treated with first-line chemotherapy.

Methods:

The PFs were identified by both logistic regression analysis and probability tree analysis in patients captured in the Soft Tissue and Bone Sarcoma Group (STBSG) database (3002 patients). Scores derived from the logistic regression analysis and algorithms derived from probability tree analysis were subsequently validated in an independent study cohort from the French Sarcoma Group (FSG) database (404 patients).

Results:

The 90-day mortality rate was 8.6 and 4.5% in both cohorts. The logistic regression analysis retained performance status (PS; odds ratio (OR)=3.83 if PS=1, OR=12.00 if PS ⩾2), presence of liver metastasis (OR=2.37) and rare site metastasis (OR=2.00) as PFs for early death. The CHAID analysis retained PS as a major discriminator followed by histological grade (only for patients with PS ⩾2). In both models, PS was the most powerful PF for 90-day mortality.

Conclusion:

Performance status has to be taken into account in the design of further clinical trials and is one of the most important parameters to guide patient management. For those patients with poor PS, expected benefits from therapy should be weighed up carefully against the anticipated toxicities.     

Functional interaction of Ugene and EBV infection mediates tumorigenic effects

Epstein-Barr virus (EBV) infection is associated with many human neoplasms, in which EBV-derived latent membrane protein-1 (LMP1) appears to be critical, but its exact oncogenic mechanism remains to be defined. To this end, our initial microarray analyses identified a LMP1-inducible gene, Ugene, originally characterized as a binding partner for uracil DNA glycosylase 2, which is highly expressed in malignant colon cancer. In this report, it was found that Ugene, designated herein as LMP1-induced protein (LMPIP), was induced, in a time-dependent manner, in EBV-infected peripheral blood mononuclear cells and LMP1-transfected 293 cells. Functionally, when compared with mock-transfected cells, overexpression of LMPIP in nasopharyngeal carcinoma (NPC) cell lines resulted in a decrease in reactive oxygen species production and maintained mitochondria membrane potential (Δψ) loss induced by H(2)O(2). The NPC cells transfected with LMPIP also showed a decrease in G1 population and an increase in the cell population in sub-G1 and multiploid phase, concomitant with increased levels of cell cycle activators, including cyclin D1 and CDK4. In contrast, silencing of LMPIP expression in the NPC tumor cell lines with short hairpin RNA interference revealed significantly decreased cell population at G1/S phase, while the number of cells in multiploid phase increased. Significantly, NPC cells with LMPIP knock-down also showed a decrease in tumorigenic and transforming activity induced by ectopic LMP1 expression, as determined by analyses of soft agar foci and tumor size in nude mice. Further, elevated LMPIP expression was also noted in cytoplasm and nuclei in EBV-infected NPC tumor cell mass and non-EBV-infected tumor cell lines. These results suggested that LMPIP may have an important mediator role in EBV-mediated neoplasm and may serve as a new target for therapy of tumors induced by EBV infection.     

Association between arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and lung function in a Korean population

Arachidonate 5-lipoxygenase-activating protein (ALOX5AP) plays a role in the 5-lipoxygenase (LO) pathway, which includes the LTC(4), LTD(4), LTE(4) and LTB(4). These leukotrienes are known causative factors of asthma, allergy, atopy and cardiovascular diseases. ALOX5AP lacks enzyme activity and acts by helping 5-LO function. In this study, healthy and general subjects who live in rural and urban areas of Korea were tested for the association of ALOX5AP polymorphisms with lung function. Lung function was also estimated by calculating the predicted values for forced expiratory volume in one second (FEV(1) _%PRED) and the proportion of the forced vital capacity exhaled in the first second (FEV(1) /FVC_PRED). The linear regression was adjusted for residence area, gender, age, height and smoking status. The analysis revealed associations between FEV(1) and the single-nucleotide polymorphism (SNP) rs9506352 and the haplotype TCAC (permuted P-value < 0.05). The linkage disequilibrium block that included the significant SNPs overlapped with SNPs that were revealed previously to associate with myocardial infarction and asthma and to affect lung function. This study is the first to demonstrate the association between lung function and ALOX5AP polymorphisms in a healthy and general population.