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Aim To evaluate the effectiveness of adjuvant treatment for morcellated, uterus-confined leiomyosarcoma in a multicenter setting. Methods We identified patients with International Federation of Gynecology and Obstetrics stage I uterine leiomyosarcoma primarily treated with surgery between 2003 and 2016. Among them, patients who underwent one of the following morcellation methods were included: (i) power morcellation; (ii) intracorporeal morcellation using scalpels or electrocautery; and (iii) vaginal morcellation. Patients' survival outcomes were compared according to the implementation of adjuvant treatment. Results From 13 institutions, 55 patients were included; 31 for adjuvant treatment group and 24 for surgery only group. The clinicopathological characteristics including the mass size, morcellation methods, extent of surgery, and mitotic count were similar between the groups. In the adjuvant treatment group, 67.7%, 19.4% and 12.9% of patients received chemotherapy, chemoradiation and radiation, respectively. After a median follow-up of 50.5 months, the adjuvant treatment and surgery only groups showed similar overall survival (5-year rate, 92.0% vs 90.4%; P = 0.959). No significant difference in progression-free survival was observed between the two groups (3-year rate, 46.1% vs 78.2%; P = 0.069). On multivariate analyses, adjuvant treatment did not affect progression-free survival (adjusted HR, 2.138; 95% CI, 0.550-8.305; P = 0.273). The adjuvant treatment group showed a trend towards more common distant metastasis, compared to the surgery only group (25.8% vs 4.2%; P = 0.062). The incidences of pelvic, retroperitoneal, and abdominal recurrences were not different between the groups. Conclusion Despite its frequent use in clinical practice, adjuvant treatment did not improve the survival outcomes of patients with morcellated, International Federation of Gynecology and Obstetrics stage I uterine leiomyosarcoma.

Objectives In sacrococcygeal teratoma, the presence of high-output cardiac failure resulting from arteriovenous shunting through the large tumor has been associated with an adverse outcome. The objective of this study was to determine whether the tumor size and cardiac biomarkers in cord blood can predict neonatal survival in sacrococcygeal teratoma. Methods The study population consisted of 25 neonates with sacrococcygeal teratoma. Tumor size was calculated by the ellipsoid formula using dimensions measured by antenatal ultrasound ([length × width × depth in cm] × 0.52= volume in cm3 ). To adjust the gestational age, the tumor volume index (tumor volume/biparietal diameter) was adopted in the analysis. Cardiac biomarkers for heart failure (N-terminal pro-B-type natriuretic peptide [NT-pro-BNP] and cardiac troponin T [cTnT]) were measured in cord blood taken at the time of delivery. Results The rate of neonatal death was 24% (6 of 25). The cases that resulted in neonatal death had a higher tumor volume index and higher concentrations of NT-pro-BNP and cTnT than those with survival. A tumor volume index of greater than 60 cm3 /cm, elevated NT-pro-BNP (>2000 pg/mL), and elevated cTnT (>0.08 ng/mL) had sensitivity of 100% for prediction of neonatal death. Conclusions The tumor volume index and cord blood biomarkers for heart failure can be promising prognostic markers for neonatal survival in sacrococcygeal teratoma.

Aim To investigate whether a concern for future pregnancy is reflected in the extent of large loop excision of the transformation zone (LLETZ) and to assess the clinical outcome. Methods We reviewed the medical records of 275 women who underwent LLETZ for precancerous lesions in cervix. We divided them into two groups according to pregnancy possibility in the future: nonpotential versus potential group. The potential group was arbitrarily defined as women who met one of the following: (i) regardless of marital status, younger than 41 years with less than two parities and (ii) regardless of parity, younger than 46 years and unmarried. After propensity score matching (1:1, 44 women in each group), we compared the extent of LLETZ with respect to short-term recurrence. Results After LLETZ, similar percentages of patients were finally diagnosed with ≥CIN3 (cervical intraepithelial neoplasia 3) in the two groups (27 [61.4%] vs 32 [72.7%], P = 0.257). Notably, the largest transverse diameter of LLETZ specimen was significantly larger in the nonpotential group (2.74 ± 1.06 vs 2.37 ± 0.62 cm, P = 0.047). There were more women with exocervical resection margin involvement in the potential group than in the nonpotential group (14 [31.8%] vs 6 [13.6%], P = 0.042). However, there was no significant difference in the incidence of short-term recurrence ≥HSIL (high-grade squamous intraepithelial lesion) within 24 months after LLETZ between the two groups (1 [2.3%] vs 1 [2.3%], P > 0.999). Conclusion Pregnancy possibility in the future may affect the extent of LLETZ, as assessed by the largest transverse diameter obtained. This finding may be associated with increased resection margin involvement in women with future pregnancy possibility.

Metformin, an oral biguanide for the treatment of type II diabetes, has been shown to have anticancer effects in ovarian cancer. Energy starvation induced by metformin causes endoplasmic reticulum stress-mediated unfolded protein response (UPR) and autophagy. UPR and autophagy act as a survival or death mechanism in cells. In this study, we observed that metformin-induced apoptosis was relieved by autophagy and the PERK/eIF2α pathway in ovarian cancer cells, but not in peripheral blood mononuclear cells (PBMC) or 'normal' ovarian surface epithelial cells (OSE). Increased PARP cleavage and increased LC3B-II with ATG5-ATG12 complex suggested the induction of apoptosis and autophagy, respectively, in metformin-treated ovarian cancer cells. Accumulation of acidic vacuoles in the cytoplasm and downregulation of p62 further supported late-stage autophagy. Interestingly, metformin induced interdependent activation between autophagy and the UPR, especially the PERK/eIF2α pathway. Inhibition of autophagy-induced PERK inhibition, and vice versa, were demonstrated using small molecular inhibitors (PERK inhibitor I, GSK2606414; autophagy inhibitor, 3-MA, and BafA1). Moreover, autophagy and PERK activation protected ovarian cancer cells against metformin-induced apoptosis. Metformin treatment in the presence of inhibitors of PERK and autophagy, however, had no cytotoxic effects on OSE or PBMC. In conclusion, these results suggest that inhibition of autophagy and PERK can enhance the selective anticancer effects of metformin on ovarian cancer cells. © 2015 Wiley Periodicals, Inc.

The endoplasmic reticulum (ER) is responsible for protein processing. In rapidly proliferating tumor cells, the ER tends to be overloaded with unfolded and misfolded proteins due to high metabolic demand. With the limited protein-folding capacity of the ER, tumor cells often suffer from more ER stress than do normal cells. Thus, cellular stress responses to cope with ER stress, such as the unfolded protein response (UPR) and autophagy, might be more activated in cancer cells than in normal cells. The complex signaling pathways from the UPR to autophagy provide promising druggable targets; a number of UPR/autophagy-targeted anticancer agents are currently in development in preclinical and clinical studies. In this short review we will discuss the potential anticancer efficacy of modulators of cellular stress responses, especially UPR and autophagy, on the basis of their signaling pathways. In addition, the current developmental status of the UPR/autophagy-targeted agents will be discussed.

Aim: There is controversy regarding the effect of obesity on the treatment and survival of ovarian cancer. This study examined the impact of obesity on the treatment and survival outcomes of epithelial ovarian cancer. Methods: The medical records of patients undergoing surgery for epithelial ovarian cancer (EOC) between January 2000 and February 2010 were reviewed. Patient demographics, surgical outcomes, clinicopathological factors and survival were evaluated and compared according to the body mass index (BMI). The Asian BMI criteria for Koreans were used. Results: Of a total of 486 patients identified, 31 (6.4%) were underweight (BMI 0.05) or overall survival (P > 0.05) according to the BMI. No difference in progression free survival (P > 0.05) or overall survival (P > 0.05) could be found, even in the subcohort of stages III and IV. Conclusion: Obesity itself does not affect the surgical and clinicopathological outcomes or even survival in EOC patients.

The poor prognosis in the treatment of ovarian cancer is mainly attributed to chemoresistance. The development of new strategies is urgently necessary to overcome chemoresistance because of the low efficacy of the current standard chemotherapy in ovarian cancer. Metabolic alterations have been suggested to have a crucial role in cancer development. The key metabolic changes in cancer include aerobic glycolysis and macromolecular synthesis, causing antiapoptosis in cancer cells. Therefore, the manipulation of the metabolic derangement could be an effective strategy to overcome chemoresistance in ovarian cancer. In this review, we will discuss metabolic interventions as promising anticancer strategies in ovarian cancer, focusing on the glycolytic, mitochondrial apoptotic, and necrotic pathways. In addition, the role of p53 in relation to metabolic alterations in cancer will be mentioned.

It is crucial to control the structure and composition of composite anode materials to enhance the cell performance of such anode materials for lithium ion batteries. Herein, a biomimetic strategy is demonstrated for the design of high performance anode materials, inspired by the structural characteristics and working principles of sticky spider-webs. Hierarchically porous, sticky, spider-web-like multiwall carbon nanotube (MWCNT) networks are prepared through a process involving ozonation, ice-templating assembly, and thermal treatment, thereby integrating the networks with γ-Fe2O3 particles. The spider-web-like MWCNT/γ-Fe2O3 composite network not only traps the active γ-Fe2O3 materials tightly but also provides fast charge transport through the 3D internetworked pathways and the mechanical integrity. Consequently, the composite web shows a high capacity of ≈822 mA h g−1 at 0.05 A g−1, fast rate capability with ≈72.3% retention at rates from 0.05 to 1 A g−1, and excellent cycling stability of >88% capacity retention after 310 cycles with a Coulombic efficiency >99%. These remarkable electrochemical performances are attributed to the complementarity of the 3D spider-web-like structure with the strong attachment of γ-Fe2O3 particles on the sticky surface. This synthetic strategy offers an environmentally safe, simple, and cost-effective avenue for the biomimetic design of high performance energy storage materials.

New (4-arylpiperazinyl)piperidines (I) and (II) have promising in vitro potency as nonpeptide BACE 1 inhibitors.