Bevacizumab increases the sensitivity of olaparib to homologous recombination-proficient ovarian cancer by suppressing CRY1 via PI3K/AKT pathway

PARP inhibitors have changed the management of advanced high-grade epithelial ovarian cancer (EOC), especially homologous recombinant (HR)-deficient advanced high-grade EOC. However, the effect of PARP inhibitors on HR-proficient (HRP) EOC is limited. Thus, new therapeutic strategy for HRP EOC is desired. In recent clinical study, the combination of PARP inhibitors with anti-angiogenic agents improved therapeutic efficacy, even in HRP cases. These data suggested that anti-angiogenic agents might potentiate the response to PARP inhibitors in EOC cells. Here, we demonstrated that anti-angiogenic agents, bevacizumab and cediranib, increased the sensitivity of olaparib in HRP EOC cells by suppressing HR activity. Most of the γ-H2AX foci were co-localized with RAD51 foci in control cells. However, most of the RAD51 were decreased in the bevacizumab-treated cells. RNA sequencing showed that bevacizumab decreased the expression of CRY1 under DNA damage stress. CRY1 is one of the transcriptional coregulators associated with circadian rhythm and has recently been reported to regulate the expression of genes required for HR in cancer cells. We found that the anti-angiogenic agents suppressed the increase of CRY1 expression by inhibiting VEGF/VEGFR/PI3K pathway. The suppression of CRY1 expression resulted in decrease of HR activity. In addition, CRY1 inhibition also sensitized EOC cells to olaparib. These data suggested that anti-angiogenic agents and CRY1 inhibitors will be the promising candidate in the combination therapy with PARP inhibitors in HR-proficient EOC

Development of Health Promotion Programs based on the Salute Genetics Model

健康社会学者のアーロン・アントノフスキー (Aaron Antonovsky) は、健康を積極的に創出する要因の研究を展開し、この成果を健康生成論 (salute genetics oriented theory) として公表した。この理論に基づくヘルス・プロモーションは、ストレス社会で生活する我々の、健康の維持・増進に寄与することが期待される。本稿では健康生成モデルに基づく、一般の人々を対象にした心理教育プログラムのあり方について論考する。健康生成志向的な認知を促すグループワークでは、①ストレスの発生、およびSOCと健康の関連についての理解を深める知識教育、② SOCの自己理解、③ SOCの改善や変容を目的にしたに取り組みなどから構成されるプログラムが考えられる。Aaron Antonovsky, who was a health sociologist, investigated factors that promoted health and then published these results as the salute genetics-oriented theory. This theory is useful for health promotion for Japanese living in stressful environments. At this article, we discussed health promotion programs based on the salute genetics-oriented model. It was concluded that the programs were constructed of three elements: education about the salute genetics-oriented and general stress models, self-understanding of “sense of coherence” (SOC), and improvement of SOC

Higuchi's transverse incision and a modification of this method for minimally invasive surgery

Study Objective: To describe Higuchi's transverse incision and a modification of this method for reduced port surgery (RPS). Design: Descriptive study. Setting: University hospital. Patients: Those with ovarian cyst and uterine myoma. Intervention: A platform is placed in the 2–3 cm Higuchi incision just above the pubis or on the pubis. Blunt dissection of the subcutaneous adipose tissue is performed. A T incision of the rectus abdominis fascia and a longitudinal incision of the peritoneum are performed. A LAP PROTECTOR and EZ access (Hakko Medical, Nagano, Japan) are used with the platform for single-incision laparoscopic surgery. The peritoneum and fascia are closed by continuous suture, and the skin is closed using the dermostitch technique. Main Results: Higuchi's transverse incision is 2–3 cm in length and is made at a much lower position than the conventional Pfannenstiel transverse incision. The wound is covered by pubic hair, yielding an excellent esthetic outcome. The T incision of the rectus abdominis fascia secures a more extensive surgical field than the Pfannenstiel transverse incision. Conclusion: Higuchi's modified transverse incision ensures a sufficient visual field, yields an excellent esthetic outcome, and is safe, suggesting the potential use of this method for RPS

Characterization of the Prediabetic State in a Novel Rat Model of Type 2 Diabetes, the ZFDM Rat

We recently established a novel animal model of obese type 2 diabetes (T2D), the Zucker fatty diabetes mellitus (ZFDM) rat strain harboring the fatty mutation (fa) in the leptin receptor gene. Here we performed a phenotypic characterization of the strain, focusing mainly on the prediabetic state. At 6–8 weeks of age, fa/fa male rats exhibited mild glucose intolerance and severe insulin resistance. Although basal insulin secretion was remarkably high in the isolated pancreatic islets, the responses to both glucose stimulation and the incretin GLP-1 were retained. At 10–12 weeks of age, fa/fa male rats exhibited marked glucose intolerance as well as severe insulin resistance similar to that at the earlier age. In the pancreatic islets, the insulin secretory response to glucose stimulation was maintained but the response to the incretin was diminished. In nondiabetic Zucker fatty (ZF) rats, the insulin secretory responses to both glucose stimulation and the incretin in the pancreatic islets were similar to those of ZFDM rats. As islet architecture was destroyed with age in ZFDM rats, a combination of severe insulin resistance, diminished insulin secretory response to incretin, and intrinsic fragility of the islets may cause the development of T2D in this strain

Laparoscopic conservative surgery for massive ovarian edema with torsion

Massive ovarian edema is a rare condition in which intermittent torsion of the ovary at its pedicle obstructs venous and lymphatic drainage and results in the development of edema in the ovarian stroma. Massive ovarian edema occurs in young women, and most women undergo oophorectomy or wedge resection of the ovary to verify the presence of a neoplasm. We report a case of massive ovarian edema with torsion in a patient who underwent laparoscopic surgery with preserved ovarian function. It is clinically important to make a diagnosis appropriately and rapidly to prevent unnecessary oophorectomy and preserve ovarian function