Individual Overall Survival Research Articles

CpG methylation analysis of the MEG3 and SNRPN imprinted genes in acute myeloid leukemia and myelodysplastic syndromes

Methylation is now established as a fundamental regulator of gene transcription. To investigate this in haematologic malignancies, we evaluated the aberrant promoter methylation of two imprinted genes (MEG3 and SNRPN) in 43 MDS and 42 AML patients. MEG3 hypermethylation occurred in 15 MDS patients (34.9%), and in 20 AML patients (47.6%). SNRPN hypermethylation was observed in 15 MDS patients (34.9%), and in 21 AML patients (50%). There were no significant correlations between WHO subtype, WPSS score, karyotype, haemoglobin levels, white blood cell count, platelet count and CpG methylation of any gene. MEG3 hypermethylation was associated with significantly reduced overall survival in individuals with AML (HR = 1.98, p = 0.04), while SNRPN CpG methylation was not associated with survival (HR = 0.94, p = 0.87). In addition, no association between survival and aberrant MEG3 (HR = 2.15, p = 0.072) or SNRPN methylation (HR = 1.08, p = 0.85) was observed in patients MDS. Our findings suggest that these genes are abnormally methylated in AML and MDS patients, and methylation of MEG3 confers worse overall prognosis. The MEG3 methylation status may serve as a useful biomarker in leukemia.

Integrating Epothilones into the Treatment of Patients with Metastatic Breast Cancer: Clinical Perspectives on Incorporating Recent Data in the Practice Setting

The introduction of modern chemotherapy agents, including the taxanes, has improved the prognosis of women with metastatic breast cancer (MBC). Ultimately, however, inevitable intrinsic or acquired resistance to chemotherapy limits treatment options. The epothilones, a novel class of microtubule-stabilizing agents that have incomplete cross-resistance with taxanes and are less susceptible to common mechanisms of resistance, have demonstrated activity in breast cancer. Ixabepilone, the best studied epothilone to date, has been approved for use as a single agent or in combination with capecitabine in anthracycline- and taxanepretreated or refractory MBC. Ixabepilone is relatively well tolerated, with the most common side effects being peripheral neuropathy and neutropenia. Other epothilones such as KOS-862, patupilone, ZK-EPO, BMS-310705, and KOS-1584 are being evaluated as therapy for patients with breast cancer, with promising preliminary data. Ongoing research aims to define and optimize the efficacy of the epothilones in an attempt to improve the quality of life and overall survival of individuals with breast cancer.

EGG MASS DRIFT INCREASES VULNERABILITY DURING EARLY DEVELOPMENT OF CASCADES FROGS (RANA CASCADAE)

Many anuran species exhibit oviposition site selection. Female selection of oviposition sites may influence the success of offspring and increase overall fitness (Resetarits 1996). Egg mass placement (location and attachment substrate) may be determined by a number of factors including detectability by predators, water velocity, risk of desiccation or flooding, and temperature (Stebbins and Cohen 1997). Some lentic breeding anurans do not always attach their egg masses to substrates (Briggs 1987; Olson 2005; Reaser and Pilliod 2005; Wind 2005), making them vulnerable to involuntary displacement. The movement of egg masses to areas of sub-optimal conditions (for example, colder water or desiccation from stranding) may affect hatching success and overall survival of individuals (Licht 1971; Sype 1974). Here, we document high occurrences of egg mass displacement in a high-elevation breeding population of Rana cascadae (Cascades Frog).