The STAT3-miRNA-92-Wnt Signaling Pathway Regulates Spheroid Formation and Malignant Progression in Ovarian Cancer.

Ovarian cancer spheroids constitute a metastatic niche for transcoelomic spread that also engenders drug resistance. Spheroid-forming cells express active STAT3 signaling and display stem cell-like properties that may contribute to ovarian tumor progression. In this study, we show that STAT3 is hyperactivated in ovarian cancer spheroids and that STAT3 disruption in this setting is sufficient to relieve chemoresistance. In an NSG murine model of human ovarian cancer, STAT3 signaling regulated spheroid formation and self-renewal properties, whereas STAT3 attenuation reduced tumorigenicity. Mechanistic investigations revealed that Wnt signaling was required for STAT3-mediated spheroid formation. Notably, the Wnt antagonist DKK1 was the most strikingly upregulated gene in response to STAT3 attenuation in ovarian cancer cells. STAT3 signaling maintained stemness and interconnected Wnt/ß-catenin signaling via the miR-92a/DKK1-regulatory pathways. Targeting STAT3 in combination with paclitaxel synergistically reduced peritoneal seeding and prolonged survival in a murine model of intraperitoneal ovarian cancer. Overall, our findings define a STAT3-miR-92a-DKK1 pathway in the generation of cancer stem-like cells in ovarian tumors, with potential therapeutic applications in blocking their progression. Cancer Res; 77(8); 1955-67. ©2017 AACR.

Primary carcinoid tumor of the ovary arising in a mature cystic teratoma: a case report.

Primary ovarian carcinoid tumors are rare entities, they may appear with other teratomatous components, and can be often being mistaken as part of mature cystic teratomas. Consistent with their rarity and low incidence, imaging clues that could have led to suspicion of this tumor are not well-documented. Herein, the authors present a rare case of primary ovarian carcinoid tumor in a mature cystic teratoma, who initially presented with complaints of abdominal distension for months. Contrast-enhanced computerized tomography (CT) demonstrated a multilobular mass with different density components including fat, soft tissue, and calcification materials, as well as rich vascular supply from the right ovarian vein. Serum tumor markers were within normal limits. Bilateral salpingo-oophorectomy was performed and the pathological diagnosis was mature cystic teratoma with coexisting primary ovarian carcinoid tumor, insular type. The patient has remained well with no residual disease for over one year of follow-up.

Inserting the tunneller during an outside-in transobturator tape procedure by syringe-needle guidance.

The objective of this study was to determine the feasibility of a novel syringe-needle guidance technique (SNG), and its impact on the perioperative variables and outcomes of patients undergoing an outside-in transobturator tape procedure (TOT). Between November 2006 and May 2008, 48 consecutive women who underwent TOT with SNG were included. Another 25 women without SNG between March 2004 and October 2006 were included as a historical control. There were no significant differences in hospital stays and complication rates between the two groups. However, the operating time was shorter (mean 23.0 vs 28.3 min, p=0.008) in the SNG group than in the control group. The presence of the SNG technique was the sole predictor of the operating time (p=0.003). In conclusion, the SNG technique is a feasible method to provide help in inserting the tunneller of TOT through the transobturator foramen, and did not compromise the outcome.

Myomectomy through the uterine cervix using forceps under sonographic guidance.

OBJECTIVES: To evaluate the feasibility of a novel method of forceps myomectomy under sonographic guidance. METHODS: Between June 2005 and August 2006, we performed a prospective study to evaluate the feasibility of forceps myomectomy under sonographic guidance in patients with submucosal myomas. Patients were enrolled into the study if, on transvaginal sonographic or hysteroscopic examination, their myomas were found to have an intramural extension < 75%, absence of 'sinking' and a mean diameter < 8 cm. RESULTS: There were 28 patients with submucosal myomas including Types 0 (n = 18), 1 (n = 6) and 2 (n = 4). In 26/28 (92.8%; 95% CI, 82.6-100) patients the myomas were removed completely. The mean operating time and intraoperative blood loss were 27.3 min and 33.5 mL, respectively. The median follow-up time was 15 months. There were no perioperative complications. No patient subsequently underwent myomectomy or hysterectomy. CONCLUSIONS: In our experience, this novel method of forceps myomectomy is feasible for the removal of Type 0 and Type 1 submucosal myomas as well as selected Type 2 myomas.

Comparison of the psychospiritual needs of Chinese heart transplant recipients at pre- and postoperative stages.

PURPOSE: This project sought to compare Chinese heart transplant (HT) recipients' psychospiritual needs during the preoperative (PS) and the postoperative predischarge stage (PDS). METHODS: Thirty HT recipients from two leading medical centers in Taiwan were recruited for this research. Data collected by face-to-face interview were analyzed by content analysis. RESULTS: The patients' ages ranged from 23 to 45 years (mean [M] +/- standard deviation [SD] = 28.5 +/- 4.1); 90% were married. The subjects' cardiac disease history ranged from 4.2 to 12.3 years (M +/- SD = 8.2 +/- 2.3). The waiting time list for HT ranged from 1.2 to 6.4 years (M +/- SD = 3.1 +/- 2.6). The subjects had the following six psychospiritual concerns: death (PS), unfulfilled family responsibilities (PS and PDS), unaccomplished personal life goals (PS and PDS), poor body image (PDS), loss of significant others' support and love (PDS), and discrimination by others (PDS). The following seven needs of help were reported: comforting the fear of failure in heart transplantation (PS and PDS), meeting unfulfilled family responsibilities (PS and PDS), accomplishing personal life goal (PS and PDS), religious support (PS and PDS), establishing confidence in body image (PDS), establishing positive relationship with significant others (PS and PDS), and preparation for dying with dignity when necessary (PS and PDS). CONCLUSION: The in-depth investigation on Chinese HT recipients' psychospiritual needs was first compared in PDS and PS. More distress and needs were found in PDS than PS. These findings were attributed by the dilemma of pursuing prospective future versus taking the risk of loss of life, valuing families' and health professionals' support system, and expecting grief and dying with dignity. Health professionals are encouraged to understand and provide stage-specific support to help them meet psycho-spiritual needs.

Three-dimensional ultrasound diagnosis of Larsen syndrome with further characterization of neurological sequelae.

Larsen syndrome consists of skeletal dysplasia with multiple joint dislocations and a characteristic facies. The basis of this abnormality is a generalized mesenchymal disorder involving connective tissues. We describe our findings in a woman who was referred at 28 weeks' gestation due to multiple fetal anomalies suspected initially at an 18-week ultrasound examination. On three-dimensional (3D) ultrasound we found the fetus had bilateral genu recurvatum. Further 3D examination at 36 weeks confirmed the lower limb anomaly and revealed facial anomalies that led to the diagnosis of Larsen syndrome. An elective Cesarean section was performed at 38 weeks' gestation to minimize neurological sequelae. Magnetic resonance imaging was performed postnatally and showed pachygyria, colpocephaly and agenesis of the corpus callosum. In this case, 3D ultrasound facilitated the prenatal diagnosis of Larsen syndrome. A careful prenatal investigation for other associated anomalies such as those of the cardiovascular or neurological systems is warranted with this diagnosis. These associated lesions are likely to have a greater impact on prognosis than the classic symptoms of Larsen syndrome and a collaborative approach is necessary to optimize delivery and postnatal management of an affected fetus.

Large pelvic accessory spleen mimicking an adnexal malignancy in a teenage girl.

A large pelvic accessory spleen in a teenage female is rare and may be misdiagnosed as an adnexal tumor. A 17-year-old girl, gravida 0, had suffered from intermittent and dull pain in the lower abdomen for 1 month. Laboratory evaluation showed a low platelet count (136,000/microL). Abdominal sonography showed a large solid mass situated at the right pelvis, containing abundant vascular supply with low resistant blood flow. At laparotomy, an accessory spleen fed by a tortuous vascular pedicle from the omentum was found and then excised. Histopathologic examination revealed congestive accessory splenomegaly. Follow-up platelet count returned to normal levels (374,000/microL). The importance of including accessory spleen in the differential diagnosis of a solid adnexal tumor with thrombocytopenia is emphasized.

In utero progressive pulmonary stenosis successfully treated with transcatheter intervention after delivery.

It is unclear whether pulmonary stenosis with intact ventricular septum is a secondary cardiac malformation. We report an infant with pulmonary stenosis (diagnosed by fetal echocardiography) with progressive obstruction in late gestation who presented with increasing transvalvular pressure gradients (15 mm Hg at 22 weeks' gestation to 47 mm Hg at 35 weeks). The tricuspid/mitral valve annulus ratio decreased from 1.25 at 24 weeks' gestation to 0.96 at 33 weeks. At 38 weeks' gestation, a male infant weighing 3,524 g, with Apgar scores of 9 and 9 at 1 and 5 minutes, respectively, was delivered by cesarean section. Critical pulmonary stenosis was confirmed by postnatal catheterization. These findings support the postulation that pulmonary stenosis is a progressive disorder. After percutaneous balloon dilatation, the transvalvular pressure gradient decreased and the right ventricular cavity increased gradually. The transvalvular pressure gradient had decreased to 15 mm Hg and the tricuspid/mitral valve annulus ratio was 0.93 at the age of 2 years.

Semilunar follicular cycle of an intertidal fish: the Fundulus model.

In their habitat, Fundulus heteroclitus (Cyprinodontidae) spawn against a variety of specific substrates that become available only at spring tides; they thus exhibit a semilunar reproductive cyclicity. In the laboratory at 28 +/- 0.6 degrees C and 14L:10D, this cyclicity is free-running and can be observed by means of daily egg collection and frequent ovarian sampling. Daily egg collection cycles gathered from three different spawning groups were pooled chronologically; the cycles were determined by nonlinear regression sine-curve matching and so were dated from Days -6 to +6, with Day 0 as the peak egg collection day. Ovaries were sampled on Days -6, -4, -2, -1, +1, +2, and +4. The pooled data indicated that early-maturing follicles (1.3- to 1.6-mm diameter) are recruited from a constant reserve of vitellogenic follicles (0.7- to 1.2-mm diameter) and become abundant early in the cycle but are depleted during Days -6 to +4 by the formation of late-maturing follicles and ovulated eggs. A midcycle peak of ovulated eggs in the ovary corresponds to the egg collection peak. This progression of follicles followed by spawning decreases the total count of the follicles (> or = 0.7-mm diameter) and eggs in the ovary by 52% (from 454 to 219 per 10 g of female weight). The semilunar follicular cycle in this Fundulus model thus includes 1) an early-cycle follicle recruitment, 2) an early- and midcycle follicle maturation, and 3) a midcycle egg ovulation and spawning. This follicular cycle also proceeds in fish deprived of a spawning substrate. A female in the wild would thus execute the follicular cycling in a timely sequence, in anticipation of each recurring spring tide, whether or not a natural substrate becomes available. We conclude that F. heteroclitus provides a useful nonmammalian model for the study of cyclic reproductive activity in the laboratory.

Freerunning circasemilunar spawning rhythm of Fundulus grandis and its temperature compensation.

Gulf killifish, Fundulus grandis, exhibit rhythmic reproductive activities that are synchronized with semilunar tidal fluctuations in their Gulf coast habitat. These cyclic activities, monitored through daily egg collections, persist in the laboratory for as long as four months with periods near the tidal period of 13.7 days. In nature, a specific semilunar spawning phase is maintained with respect to tidal cycles. However, in the laboratory, the phase may gradually advance or delay. These phase changes occur as a result of small differences between the periods of the spawning cycle and concurrent tidal cycle. Changes in the phase of the spawning cycle can be produced after several cycles by exposing fish to different temperatures (21 and 27°C). However, the period of the spawning cycle changes only slightly with temperature. Q10 calculations produce a value not significantly different from 1.0, indicating nearly complete temperature compensation. These results provide evidence for an endogenous circasemilunar cycle that is temperature-compensated and freeruns in the laboratory.