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Growing teratoma syndrome (GTS) is rare clinical phenomenon occurring as a sequelae of a malignant germ cell tumor. We present the case of a 20-year-old woman who developed GTS after undergoing fertility-sparing surgery and chemotherapy for an immature teratoma. She underwent left salpingo-oophorectomy, right ovarian cystectomy, and disseminated tumor reduction during her primary surgery. The postsurgical histology report identified the tumor as an immature teratoma, grade 3, International Federation of Gynecology and Obstetrics (FIGO) stage IIIb. She subsequently received 3 cycles of chemotherapy consisting of bleomycin, etoposide, and cisplatin. At 17 months after the chemotherapy, follow-up computed tomography (CT) scan revealed an enlarged mass in her right paracolic gutter and a small peritoneal lesion in the pouch of Douglas. Her serum alpha-fetoprotein level was not elevated. These findings were compatible with GTS, but it was difficult to rule out a recurrent immature teratoma. Diagnostic exploratory laparoscopic surgery revealed the enlarged tumors that had been detected by the CT scan. Although there were multiple tumors in the pouch of Douglas, we were able to resect all of them laparoscopically. Histological diagnosis of the surgically resected specimens was of a mature teratoma, and so we concluded that this tumor was a GTS. Our experience suggests that laparoscopic surgery is an effective alternative diagnostic and therapeutic approach in cases suspicious of GTS where the disease is disseminated to the peritoneum. [ABSTRACT FROM AUTHOR]

Abstract: Therapeutic targeting of angiogenesis has become a novel approach to cancer therapy. The recent discovery of specific molecular targets that modulate the endothelial cell response and the development of suitable methods for assessing the contribution of these targets have given further impetus for the development and therapeutic application of an angiogenesis‐targeted therapy. The small GTPase Rho and the major downstream effector, Rho kinase, is well established to regulate cell migration by the formation of stress fibers and the turnover of focal adhesions and plays a pivotal role in endothelial cell organization in angiogenesis. Several approaches have been developed to analyze the contribution of Rho kinase so far, and this chapter describes the in vitro and in vivo protocols used routinely in our laboratory to analyze the contribution in angiogenesis and shows the possibility of Rho kinase inhibitors in the clinical setting. [Copyright &y& Elsevier]

The procoagulatory serine protease, thrombin, is known to induce invasion and metastasis in various cancers, but the mechanisms by which it promotes tumorigenesis are poorly understood. Because the 92-kDa gelatinase (MMP-9) is a known mediator of tumor cell invasion, we sought to determine whether and how thrombin regulates MMP-9. The thrombin receptor, PAR-1, and MMP-9 are expressed in osteosarcomas, as determined by immunohistochemistry. Stimulation of U2-OS osteosarcoma cells with thrombin and a thrombin receptor-activating peptide induced pro-MMP-9 secretion as well as cell surface-associated pro-MMP-9 expression and proteolytic activity. This was paralleled by an increase in MMP-9 mRNA and MMP-9 promoter activity. Thrombin-induced invasion of U2-OS cells through Matrigel was mediated by the phosphatidylinositol 3-kinase signaling pathway and could be inhibited with an MMP-9 antibody. The stimulation of MMP-9 by thrombin was paralleled by an increase in β1-integrin mRNA and β1-integrin expression on the cell surface, which was also mediated by phosphatidylinositol 3-kinase and was required for invasion. Thrombin activation induced and co-localized both β1-integrin and pro- MMP-9 on the cell membrane, as evidenced by co-inimunoprecipitation, confocal microscopy, and a protein binding assay. The thrombin-mediated association of these two proteins, as well as thrombin-mediated invasion of U2-OS cells, could be blocked with a cyclic peptide and with an antibody preventing binding of the MMP-9 hemopexin domain to β1-integrin. These results suggest that thrombin induces expression and association of β1-integnn with MMP-9 and that the cell surface localization of the protease by the integrin promotes tumor cell invasion. [ABSTRACT FROM AUTHOR]

Objective: A forearm fracture (Colles' fracture) is often the first sign of osteoporosis and should alert the patient and physician to the possibility of underlying skeletal fragility. Therefore, the establishment of a more accurate and reliable method for the measurement of bone mineral density (BMD) at the distal radius would be beneficial for the patients who suffer from osteoporosis. The objective of the present study was to evaluate the usefulness of peripheral quantitative computed tomography (pQCT) to assess the change of BMD at the distal radius in early postmenopausal women who receive hormone replacement therapy (HRT). Methods: Twenty healthy early postmenopausal women who were diagnosed as osteoporosis or osteopenia were randomized to either HRT or placebo treatment. We analyzed BMD of the distal radius by pQCT, lumbar spine by dual-energy X-ray absorptiometry (DXA) and the biochemical markers of bone turn over (osteocalcin, deoxypyridinoline) every 6 months. Results: The placebo group showed a significant decrease from the baseline in the trabecular BMD of the radius at 12 months (7.4+/-2.5%) (p<0.05), whereas the HRT group showed a slight increase (0.7+/-2.2%). The changes in the trabecular BMD of the radius between the HRT and placebo groups were statistically different at 12 months (p<0.05). On the other hand, in the cortical BMD of the radius, no significant differences were seen between the changes of bone densities in the HRT and control groups after 1 year of treatment. pQCT could detect a significant loss of BMD of the radius in early postmenopausal women after 1 year and HRT prevented its loss. Conclusion: Our preliminary clinical trial showed that pQCT might be useful for the early detection of bone loss in early postmenopausal women and for the monitoring BMD of the patients who receive HRT. [ABSTRACT FROM AUTHOR]

The small guanosine triphosphatase RhoA/Rho-kinase cascade has been implicated in uterine contraction. Our purpose was to evaluate the tocolytic effect of a Rho-kinase inhibitor, Y-27632, in lipopolysaccharide-induced preterm delivery in mice. Study design: We used an animal model of lipopolysaccharide-induced preterm delivery in C3H/ HeN × B6D2F1 pregnant mice. Y-27632 was delivered continuously through an osmotic pump that was implanted into the peritoneal cavity 6 hours before lipopolysaccharide treatment. The primary outcome was the preterm delivery rate. To further study the possible involvement of this cascade in lipopolysaccharide-induced preterm delivery, we determined the effect of lipopolysaccharide and prostaglandin F2α on RhoA activation in mouse myometrial cells and uterine smooth muscle tissues. Results: The rate of preterm delivery for lipopolysaccharide-treated animals was 94.4%. The administration of Y-27632 (1 or 10 mg/kg/d) significantly reduced the preterm delivery rate to 61.1% or 15.8%, respectively. The level of guanosine triphosphate bound RhoA was increased after the addition of lipopolysaccharide or prostaglandin F2α. Conclusion: The RhoA/Rho-kinase cascade is involved in lipopolysaccharide-induced preterm delivery, which suggests that Rho-kinase could be used as a new therapeutic target for the prevention of preterm labor. [ABSTRACT FROM AUTHOR]

Uterine tumor resembling ovarian sex-cord tumors (UTROSCT) is an extremely rare type of uterine tumor, and its clinical characteristics are not fully understood. A systematic literature search was conducted in PubMed and MEDLINE using the keywords, “uterine tumors resembling ovarian sex cord tumors”, limited to case reports. Clinico-pathological characteristics and survival data were abstracted and evaluated for the analysis. Among 43 cases reporting UTROSCT, Type I (endometrial stromal tumors with sex cord-like elements, ESTSCLE) and Type II (classic UTROSCT) were reported in 5 (11.6%) and 17 (39.5%), respectively, and nearly half of reported UTROSCT did not subcategorize the histology pattern into Type I or II (unspecified, n = 21, 48.8%). Mean age was 52.2. The two most common symptoms were postmenopausal vaginal bleeding (44.2%) and abnormal menstruation (39.5%). The majority underwent total hysterectomy with adnexectomy (65.1%) followed by hysterectomy alone (18.6%) and tumor resection alone (14.0%). Mean tumor size was 6.2 cm, and extra-uterine spread was seen in 7.0%. By immunohistochemistry, calretinin expression was significantly correlated with CAM5.2, inhibin, and progesterone receptor expression (all, p < 0.05). In survival analysis, disease-free survival (DFS) rates for all 43 cases at 1, 2, and 5 years for all cases were 97.0%, 92.7%, and 69.7%, respectively. Among recurrent cases, median time to recur was 24 months (range 9–48). Decreased DFS was significantly associated with pelvic pain (2-year rate, 81.8% versus 94.7%, p = 0.006), histology subcategory (Type I versus II, 23.8% versus 100%, p = 0.006), tumor size ≥10 cm (75.0% versus 100%, p = 0.046), cervical/extra-uterine metastasis (46.7% versus 100%, p = 0.024), and lymphovascular space involvement (50% versus 100%, p = 0.002). Treatment patterns were not statistically associated with DFS (hysterectomy, p = 0.28; and adnexectomy, p = 0.38). When histology patterns were examined, Type II disease was associated with less aggressive tumor behavior when compared to Type I disease: extra-uterine spread (Type I versus II, 40% versus 5.9%, p = 0.007) and lymphovascular space invasion (50% versus 6.7%, p = 0.012). Among 17 cases of Type II disease, disease recurrence was reported in 1 (5.9%) case at 3 years after the initial treatment. In conclusion, our study showed that UTROSCT was often not subcategorized. Because classic UTROSCT has a distinct clinical outcome and characteristic histological patterns when compared to ESTSCLE, distinguishing UTROSCT from ESTSCLE is an integral component of the diagnosis. While classic UTROSCT typically has a favorable prognosis, it has been known to develop a late recurrence. If risk factors for recurrence are absent, both hysterectomy and mass resection alone are possible options for management. [ABSTRACT FROM AUTHOR]

Objectives: Estrogen acts directly on endothelial nitric oxide synthase through a non-genomic mechanism, resulting in rapid dilatation of blood vessels. In this study, we examined the change of endothelial function after surgical menopause.Methods: In 20 subjects who underwent gynecological operations (ovariectomy (OVX) 12, sham (SHAM) operation 8), postoperative changes of flow-mediated dilatation (FMD) of the brachial artery were examined using ultrasonography. Postoperative changes of the response to nitroglycerin (NTG) were also studied in these patients.Results: In the OVX group, significant decreases of FMD were observed 1 week after the operation, although no changes were observed in the response to NTG. In the SHAM group, no remarkable changes of FMD or the response to NTG were observed after the operation.Conclusions: OVX influences endothelium-dependent vasodilatation within as little as 1 week. Therefore, it may be important to address the rapid changes of circulation after surgical menopause in order to prevent cardiovascular disease. [ABSTRACT FROM AUTHOR]