The past few years have seen an explosion of interest in the epigenetics of cancer. This has been a consequence of both the exciting coalescence of the chromatin and DNA methylation fields, and the realization that DNA methylation changes are involved in human malignancies. The ubiquity of DNA methylation changes has opened the way to a host of innovative diagnostic and therapeutic strategies. Recent advances attest to the great promise of DNA methylation markers as powerful future tools in the clinic.

The power and the promise of DNA methylation markers

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, with a prevalence of up to 10%. Various diagnostic criteria have been proposed, generally centered around the features of hyperandrogenism and/or hyperandrogenemia, oligo-ovulation and polycystic ovarian morphology. Insulin resistance is present in a majority of cases, with compensatory hyperinsulinemia contributing to hyperandrogenism via stimulation of ovarian androgen secretion and inhibition of hepatic sex hormone-binding globulin production. Adipose tissue dysfunction has been implicated as a contributor to the insulin resistance observed in PCOS. Environmental and genetic factors also have a role in the development of PCOS. The syndrome is associated with numerous morbidities, including infertility, obstetrical complications, type 2 diabetes mellitus, cardiovascular disease, and mood and eating disorders. Despite these morbidities, PCOS may be common in our society owing to evolutionary advantages of the syndrome in ancient times, including smaller family sizes, reduced exposure to childbirth-related mortality, increased muscle mass and greater capacity to store energy. The diagnosis of PCOS hinges on establishing key features while ruling out other hyperandrogenic or oligo-ovulatory disorders. Treatment is focused on the goals of ameliorating hyperandrogenic symptoms, inducing ovulation and preventing cardiometabolic complications.

Polycystic ovary syndrome: etiology, pathogenesis and diagnosis

Objectives To assess the evidence for the clinical effectiveness of ultrasound guided central venous cannulation. Data sources 15 electronic bibliographic databases, covering biomedical, science, social science, health economics, and grey literature. Design Systematic review and meta-analysis of randomised controlled trials. Populations Patients scheduled for central venous access. Intervention reviewed Guidance using real time two dimensional ultrasonography or Doppler needles and probes compared with the anatomical landmark method of cannulation. Data extraction Risk of failed catheter placement (primary outcome), risk of complications from placement, risk of failure on first attempt at placement, number of attempts to successful catheterisation, and time (seconds) to successful catheterisation. Data synthesis 18 trials (1646 participants) were identified. Compared with the landmark method, real time two dimensional ultrasound guidance for cannulating the internal jugular vein in adults was associated with a significantly lower failure rate both overall (relative risk 0.14, 95% confidence interval 0.06 to 0.33) and on the first attempt (0.59, 0.39 to 0.88). Limited evidence favoured two dimensional ultrasound guidance for subclavian vein and femoral vein procedures in adults (0.14, 0.04 to 0.57 and 0.29, 0.07 to 1.21, respectively). Three studies in infants confirmed a higher success rate with two dimensional ultrasonography for internal jugular procedures (0.15, 0.03 to 0.64). Doppler guided cannulation of the internal jugular vein in adults was more successful than the landmark method (0.39, 0.17 to 0.92), but the landmark method was more successful for subclavian vein procedures (1.48, 1.03 to 2.14). No significant difference was found between these techniques for cannulation of the internal jugular vein in infants. An indirect comparison of relative risks suggested that two dimensional ultrasonography would be more successful than Doppler guidance for subclavian vein procedures in adults (0.09, 0.02 to 0.38). Conclusions Evidence supports the use of two dimensional ultrasonography for central venous cannulation.

https://www.bmj.com/content/bmj/327/7411/361.full.pdf

Ultrasonic locating devices for central venous cannulation: meta-analysis.

Pancreatic adenocarcinoma is the most lethal of the solid tumors and the fourth leading cause of cancer-related death in North America. Most patients present with locally advanced or metastatic disease that precludes curative resection. These patients have an extremely poor prognosis. In the absence of effective screening methods, considerable efforts have been made during the past decade to identify better systemic treatments. Unfortunately most trials have not shown a survival advantage for most therapies. In tandem with this increased clinical research, there has also been an expansion of preclinical laboratory investigation. These preclinical studies revealed many of the molecular mechanisms involved in pancreatic cancer development, which has provided insights into why current therapies are ineffective. These new discoveries provide some optimism that new agents inhibiting specific targets will improve outcome and overcome the resistance of pancreatic cancer to most standard treatments. We review the current standards of care for patients with locally advanced and metastatic pancreatic carcinoma and outline some future directions for the development of new treatment strategies.

Advanced pancreatic carcinoma: current treatment and future challenges.

We report studies of preimplantation human embryo development that correlate time-lapse image analysis and gene expression profiling. By examining a large set of zygotes from in vitro fertilization (IVF), we find that success in progression to the blastocyst stage can be predicted with >93% sensitivity and specificity by measuring three dynamic, noninvasive imaging parameters by day 2 after fertilization, before embryonic genome activation (EGA). These parameters can be reliably monitored by automated image analysis, confirming that successful development follows a set of carefully orchestrated and predictable events. Moreover, we show that imaging phenotypes reflect molecular programs of the embryo and of individual blastomeres. Single-cell gene expression analysis reveals that blastomeres develop cell autonomously, with some cells advancing to EGA and others arresting. These studies indicate that success and failure in human embryo development is largely determined before EGA. Our methods and algorithms may provide an approach for early diagnosis of embryo potential in assisted reproduction.

研之平塚

Papers

結腸癌術後の早期離床・早期経口摂取に関するProspective Randomized Trial

CGH-array (Comparative Genomic Hybridization-Array) による大腸癌肝転移巣の遺伝子学的解析 : 肝転移関連遺伝子の探求ならびに臨床応用への可能性

研之 平塚

Papers

結腸癌術後の早期離床・早期経口摂取に関するProspective Randomized Trial

CGH-array (Comparative Genomic Hybridization-Array) による大腸癌肝転移巣の遺伝子学的解析 : 肝転移関連遺伝子の探求ならびに臨床応用への可能性

研之平塚