A Case Report of Occult Breast Cancer Detected by Diagnostic Laparoscopy for Suspected Ovarian Cancer.

Diagnostic laparoscopy is useful in the management of gynecological cancers; however, it can occasionally result in the detection of other malignancies. Occult breast cancer (OBC) is metastatic breast cancer without a recognized primary breast lesion. We report a rare case of OBC that was detected laparoscopically. A 64-year-old female presented to our hospital with back pain. Magnetic resonance imaging (MRI) revealed a 50 mm multicystic tumor with an internal nodule in the right ovary. Positron emission tomography/computed tomography showed abnormal accumulation in multiple lymph nodes, moderate accumulation in the ovarian tumor nodule, and no accumulation in the breasts. Ovarian cancer was suspected, and a diagnostic laparoscopy was performed. Laparoscopically, a cystic tumor in the right ovary and 10 mm nodule in the right round ligament were observed and partially resected. Immunohistopathologically, the nodules of the round ligament exhibited features consistent with those of breast cancer, but the ovarian tumor was a seromucinous borderline tumor. MRI revealed no breast lesions. Therefore, the malignancy was diagnosed as an OBC.

Hepcidin as a key regulator of iron homeostasis triggers inflammatory features in the normal endometrium.

Menstrual blood, containing high iron levels, can undergo retrograde transport into the abdominal cavity. Excess iron causes oxidative stress and inflammation. Iron metabolism is regulated by hepcidin, and serum hepcidin levels are increased in patients with endometriosis; however, the functions of hepcidin in normal endometrium remain unclear. We therefore aimed to examine hepcidin concentrations in patients with endometriosis and to determine if iron accumulation and hepcidin increased the production of reactive oxygen species (ROS) and inflammation in normal endometrial cells. We determined hepcidin levels in peritoneal fluid and menstrual blood from patients with and without endometriosis (25/16 and 15/15 patients, respectively). We also examined the effects of hepcidin on ferroportin expression, iron accumulation, and ROS generation in normal endometrial stromal cells (NESCs) from 20 women who underwent surgery for uterine leiomyoma, using immunohistochemistry and immunofluorescence analyses and analyzed its effect on the expression of inflammatory cytokines by real-time polymerase chain reaction. There was no significant difference in iron concentrations in menstrual blood or peritoneal fluid between women with and without endometriosis; however, women with endometriosis had significantly higher hepcidin levels in menstrual blood. Hepcidin reduced the expression of ferroportin in NESCs and promoted the accumulation of ferrous iron. Hepcidin plus ferrous iron increased the production of ROS and inflammatory cytokines compared with ferrous iron alone. These results indicate that women with endometriosis have high hepcidin levels in menstrual blood, leading to increased iron production, oxidative stress, and inflammation, which may, in turn, promote the development of endometriosis.

Successful resection of growing teratoma syndrome in the abdominal wall with reconstruction using tensor fascia lata muscle flap: A case report and literature review.

While cancer cure is the primary goal, fertility preservation is also a cornerstone of the underlying principle of treatment for ovarian germ cell tumors. Growing teratoma syndrome (GTS) presents with growth of mature teratomas during or after chemotherapy. We report a case of successful treatment of GTS in the anterior abdominal wall involving reconstruction. A 23-year-old woman with a suspected right ovarian mature teratoma with torsion underwent emergency laparoscopically assisted extracorporeal ovarian cystectomy. Histopathological findings revealed a grade 1 immature teratoma. After two months, postoperative α-fetoprotein (AFP) levels increased, and disseminated lesions developed not only in the pelvic cavity but also in the abdominal wound where the tumor had been extracted using an extracorporeal technique at the time of primary surgery. The patient underwent laparoscopic right salpingo-oophorectomy, excision of multiple peritoneal nodules, and biopsy of abdominal wall mass. The left rectus abdominis muscle tumor could not be removed. All of these nodules were diagnosed as metastatic immature teratomas. Although the patient received three cycles of chemotherapy, the residual tumor in the abdominal wall grew remarkably despite post-chemotherapy normalization of AFP levels. Both rectus abdominis muscles involving the residual tumors were removed and reconstructed using a left tensor fascia lata muscle flap. Histopathologically, the residual tumors were identified as mature teratomas with no immature elements, resulting in GTS. The patient got pregnant without the need of fertility treatment and gave birth uneventfully by cesarean section. Thus, reconstruction with a tensor fascia lata muscle flap facilitated complete removal of GTS while preserving fertility.

Low-Nutrient Environment-Induced Changes in Inflammation, Cell Proliferation, and PGC-1α Expression in Stromal Cells with Ovarian Endometriosis.

Although nutrient status plays an important role in cell metabolism, its significance in endometriosis is obscure. Herein, we investigated the effects of a low-nutrient microenvironment on endometriosis. Stromal cells (SCs) from ovarian endometrioma (OESCs) or normal endometrium without endometriosis (NESCs) were isolated and cultured. A low-nutrient microenvironment was replicated by replacing the culture medium with Hank's balanced salt solution. OESC and NESC proliferation under the low-nutrient condition was measured. The expression of exacerbating factors in endometriosis under the low-nutrient condition was examined at the mRNA and protein levels. OESCs showed higher proliferation than NESCs under the low-nutrient condition. In OESCs, the low-nutrient condition upregulated the mRNA expression of vascular endothelial growth factor (VEGF), interleukin-6 and -8, aromatase, Bcl-2, and peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and downregulated that of BAX and induced transcription of PI.3, PII, and exon II. Western blotting revealed elevated VEGF and PGC-1α expression under the low-nutrient condition in OESCs. These changes coincided with the elevated expression of PGC-1α, which was reduced at the mRNA level upon nutrient status rescue. Endometriosis is exacerbated by altered angiogenesis, inflammation, anti-apoptosis, and local estrogen production while trying to survive under a low-nutrient microenvironment; it may be attributed to PGC-1α-mediated metabolic mechanisms.

Giant retroperitoneal dedifferentiated liposarcoma mimicking ovarian cancer: A case report.

Retroperitoneal liposarcoma is a rare tumor, and its dedifferentiated subtype and a larger diameter are associated with a poor prognosis. However, there are few reports of retroperitoneal liposarcomas, both with a dedifferentiated subtype and a diameter of >30 cm. We report a case of a giant retroperitoneal liposarcoma with a dedifferentiated subtype. A 78-year-old woman presented to our hospital with abdominal distension and loss of appetite. Computed tomography and magnetic resonance imaging findings revealed a 35-cm-diameter solid tumor in the peritoneal cavity. CA125 (64.8 U/mL) and HE4 (229.0 pmol/L) were elevated preoperatively raising suspicion for ovarian malignancy. However, intraoperative findings revealed that the tumor originated in the retroperitoneal cavity. Reductive surgery for the tumor and partial resection of the sigmoid colon and left ureter were performed, and pathological examination confirmed a retroperitoneal dedifferentiated liposarcoma. Although her symptoms improved postoperatively, she died 11 months after surgery due to disease progression.

Successful nedaplatin desensitization therapy in a patient with platinum-sensitive recurrent ovarian cancer: A case report and literature review.

Desensitization protocols of platinum-based agents are recommended for patients with a history of hypersensitivity reaction (HSR). Herein, we report the first case of a successful desensitization therapy with nedaplatin after HSR to carboplatin and nedaplatin for platinum-sensitive recurrent ovarian cancer. A 53 year-old woman was diagnosed with stage IIIC serous carcinoma of the ovary and underwent primary debulking surgery followed by an adjuvant chemotherapy. The tumor relapsed 4 times in 10 years after the initial treatment, and platinum-based chemotherapy was performed on each occasion. HSR to carboplatin without and with desensitization protocol occurred during the 9th cycle of treatment and 2nd cycle of retreatment, respectively. Additionally, HSR to nedaplatin occurred during the 16th cycle of nedaplatin treatment. A four-step desensitization protocol with nedaplatin was conducted without occurrence of any severe adverse event. Nedaplatin desensitization regimen could be a new alternation for HSR to platinum-based agents.

Genistein induces long-term expression of progesterone receptor regardless of estrogen receptor status and improves the prognosis of endometrial cancer patients.

Progesterone is used to treat uterine endometrial cancer in young patients wishing to preserve their fertility as well as in advanced or recurrent patients, but its response rate is limited. The antitumor effect of progesterone is mediated by progesterone receptor (PR) binding. Hence, loss of progesterone's therapeutic effect, i.e., development of progesterone resistance, is mainly due to decreased PR expression. However, little is known about underlying mechanisms that regulate PR expression. Immunohistochemistry analysis of specimens from 31 young, endometrial cancer patients showed that elevated PR expression significantly increased (P < 0.05) rates of progression-free and overall survival. We investigated mechanisms of regulating PR expression and suppressing cell proliferation using genistein, a chemotherapeutic agent against different cancers. Genistein inhibits cell growth by inducing cell cycle arrest in G2 and apoptosis; moreover, it upregulates prolonged expression of PR-B and forkhead box protein O1, regardless of estrogen receptor alpha expression in endometrial cancer cells. Genistein-induced PR expression decreases CCAAT/enhancer binding protein beta expression and activates c-Jun N-terminal kinase pathway, rather than causing epigenetic alterations of the PR promoter. Therefore, increased PR expression is an important antitumor effect of genistein. This may help to improve the response rates of fertility-sparing treatments for young patients.

Progesterone Receptor Status of Epithelial Cells as a Predictive Marker for Postoperative Recurrence of Endometriosis.

CONTEXT: Progesterone resistance including progesterone receptor (PR) deficiency contributes to the pathophysiology of endometriosis; however, whether the PR expression levels in ovarian endometrioma (OE) correlate with the postoperative recurrence of endometriosis remains unclear. OBJECTIVE: This study aimed to investigate the association between PR expression levels in OE and the recurrence of endometriosis. METHODS: OE specimens were obtained from 132 patients who underwent conservative surgery for endometriosis. The PR expression levels were evaluated using the H score after immunohistochemical staining. RESULTS: Of the 132 patients, 36 (27.3%) experienced recurrence and 96 (72.7%) did not. No differences were observed in the patient characteristics between the recurrence and nonrecurrence groups except for follow-up period. PR immunoreactivity in the epithelial cells (ECs) was statistically significantly lower in the recurrent group than in the nonrecurrent group (P < .01); however, this change was not observed in the stromal cells. Moreover, multivariable logistic regression analysis revealed that the H score of PR in ECs was an independent factor and was statistically significantly associated with the recurrence of endometriosis (P = .01). Furthermore, we divided the patients into PR-negative or PR-positive groups. The cumulative recurrence rate in the negative PR group was statistically significantly higher than that in the positive PR group (P = .046). CONCLUSION: Low PR expression levels in OE-ECs may predict the recurrence of endometriosis. The PR status in OE-ECs is associated with the pathophysiology of the recurrence of endometriosis, and optimized postoperative management for endometriosis may be provided by referring to the PR status.

3D-Image-Guided Multi-Catheter Interstitial Brachytherapy for Bulky and High-Risk Stage IIB-IVB Cervical Cancer.

This study aimed to evaluate the efficacy and safety of computed tomography-magnetic resonance imaging (CT-MRI)-guided multi-catheter interstitial brachytherapy for patients with bulky (≥4 cm) and high-risk, stage IIB-IVB advanced cervical cancer. Eighteen patients who underwent concurrent chemoradiotherapy with multi-catheter interstitial brachytherapy between September 2014 and August 2020 were enrolled. The prescribed dose of external beam radiotherapy was 45-50.4 Gy, and the brachytherapy high-dose-rate aim was 25-30 Gy per 5 fractions. The endpoints were four-year local and pelvic control rates, four-year disease-free and overall survival rates, and the adverse events rate. The median follow-up period was 48.4 months (9.1-87.5 months). Fifteen patients received concurrent cisplatin therapy (40 mg/m2, q1week). Four (22.2%), seven (38.9%), and seven (38.9%) patients had stage II, III, and IV cervical cancer, respectively. Pelvic and para-aortic lymph node metastases were observed in 11 (61.1%) and 2 (11.1%) patients, respectively. The median pre-treatment volume was 87.5 cm3. The four-year local control, pelvic control, disease-free survival, and overall survival rates were 100%, 100%, 81.6%, and 87.8%, respectively. Three (16.7%) patients experienced grade 3 adverse events, and none experienced grade 4-5 adverse events. CT-MRI-guided multi-catheter interstitial brachytherapy could be a promising treatment strategy for locally advanced cervical cancer.

Successful detection of rectal injury during laparoscopic surgery using a rectal probe in a patient with deep endometriosis.

Laparoscopic surgery has become the gold standard treatment for endometriosis. Surgical treatment of deep endometriosis with colorectal involvement is challenging. It requires complete surgical excision of lesions despite a high risk of complications that include rectal injury, rectovaginal fistula and pelvic abscess. An intraoperative air leak test allows detection of rectal injury and reduces postoperative complications. We report a case of successful management of rectal injury during laparoscopic surgery using a rectal probe even though air leak tests were negative. A 45-year-old woman with severe endometriosis and rectal involvement underwent total laparoscopic hysterectomy combined with rectal shaving. A pinhole injury that reached the rectal muscularis layer without breaching the mucosal layer was identified using a rectal probe after negative air leak tests. The injury was repaired uneventfully. Our experience suggests that using a rectal probe could be helpful for early detection and safe repair of rectal injury during surgery.

Interleukin-9 produced by helper T cells stimulates interleukin-8 expression in endometriosis.

PROBLEM: Inflammation and immune responses play crucial roles in the development of endometriosis. Although interleukin-9 (IL-9) has a pro-inflammatory function in chronic inflammatory diseases, its function in endometriosis remains unknown. Here, we aimed to investigate the significance of IL-9 and IL-9-producing lymphocytes in endometriosis. METHOD OF STUDY: Specimens were obtained from patients with and without endometriosis. Peritoneal fluid (PF), peripheral blood (PB), and ovarian endometrioma (OE) tissues were analyzed for the proportion of CD4+ IL-9+ lymphocytes and IL-9 concentration using flow cytometry and enzyme-linked immunosorbent assay. OE, endometrium with endometriosis (EE), and normal endometrium (NE) were analyzed for IL-9 receptor (IL-9R) expression using immunohistochemical staining. IL-9-dependent changes in Interleukin-8 (IL-8) expression in endometrial stromal cells from OE (OESCs) were evaluated using real-time PCR. RESULTS: The proportion of CD4+ IL-9+ lymphocytes was higher in the PF, but not the PB, of patients with endometriosis than individuals without endometriosis (p < .05). However, IL-9 levels in the PF did not differ between those with and without endometriosis. We detected CD4+ IL-9+ lymphocytes in OE tissues and IL-9R in OE tissues and OESCs. In OESC culture, IL-9 significantly elevated IL-8 expression in a dose-dependent manner (p < .05), which was nullified by the addition of the anti-IL-9 receptor antibody. Furthermore, IL-9 additively stimulated IL-8 expression in the presence of TNF-α (p < .05). CONCLUSION: Our findings show that IL-9 produced by helper T cells induces IL-8 expression, suggesting that IL-9 plays an important role in the development of endometriosis by stimulating IL-8 expression.

Atherosclerosis-related biomarkers in women with endometriosis: The effects of dienogest and oral contraceptive therapy.

OBJECTIVE: Chronic inflammation in endometriosis is associated with increased risk of future cardiovascular disease; however, no studies have investigated the cardiovascular risk of women who have undergone hormonal therapy for endometriosis. We investigated atherosclerosis-related biomarkers in women with and without endometriosis and the effects of dienogest (DNG) and oral contraceptive (OC) therapies. STUDY DESIGN: In this cross-sectional study, 109 women with endometriosis and 42 control women without endometriosis were enrolled. The endometriosis group was divided into the untreated (n = 34), DNG therapy (n = 33), and OC therapy (n = 42) groups. Lipid profile serum levels, inflammatory marker such as high-sensitivity C-reactive protein, oxidative stress markers such as oxidized low-density lipoprotein and diacron-reactive oxygen metabolites, and atherosclerosis indicators (cardio-ankle vascular index [CAVI] and ankle-brachial pressure index [ABI]) were measured. RESULTS: The median treatment duration was 28 months in the DNG group and 32.5 months in the OC group. Triglyceride levels were higher in the OC group than in the other three groups (P < 0.05). Regarding markers of inflammation and oxidative stress, log high-sensitivity C-reactive protein and diacron-reactive oxygen metabolites levels were higher in the untreated group than in the control group (P < 0.05), and these markers were further increased in the OC group (log high-sensitivity C-reactive protein: P < 0.05; diacron-reactive oxygen metabolites: P < 0.01), but not in the DNG group. There was no difference in the CAVI and ABI among all groups. Spearman correlation revealed a positive correlation between duration of OC therapy and CAVI (ρ = +0.49; P = 0.002), but no correlation between the duration of DNG therapy and CAVI (ρ = -0.04; P = 0.81). CONCLUSIONS: Inflammation and oxidative stress markers are increased in women with untreated endometriosis. Treatment with OC, but not with DNG, further increases these levels. There was a positive association between the duration of OC administration and atherosclerosis risk for women with endometriosis. Our results suggest that DNG could be administered to endometriosis without the increased atherosclerosis risk and short-term OC administration for endometriosis is not harmful, however, atherosclerosis risk should be strictly observed.

Estrogen-related receptor alpha induces epithelial-mesenchymal transition through cancer-stromal interactions in endometrial cancer.

Estrogen-related receptor alpha (ERRα), which shares structural similarities with estrogen receptors, is associated with tumor progression in endometrial cancer, but little is known about the detailed underlying mechanism. We investigated whether ERRα, in cooperation with peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), could participate in epithelial-mesenchymal transition (EMT) in endometrial cancer through cancer-stromal interactions. Two endometrial cancer cell lines, Ishikawa and HEC-1A, transfected with ERRα/PGC-1α expression plasmids or silenced for ERRα expression, were co-cultured with telomerase-transformed human endometrial stromal cells (T-HESCs). We found that EMT-associated factors including vimentin, Snail, and zinc finger E-box binding homeobox 1 were upregulated in cancer cells overexpressing ERRα/PGC-1α and that transforming growth factor-beta (TGF-ß) was induced in T-HESCs in the same conditions. In contrast, ERRα knockdown suppressed EMT-associated factors in cancer cells and TGF-ß in T-HESCs. ERRα/PGC-1α overexpression increased the expression of EMT-associated factors after TGF-ß exposure; however, it decreased E-cadherin at protein level. ERRα knockdown suppressed EMT-associated factors in the presence of TGF-ß, whereas E-cadherin remained unchanged. Matrigel invasion assays revealed that ERRα knockdown attenuated the stimulation of migration and invasion by TGF-ß. These findings suggest that ERRα is a potential target for inhibiting TGF-ß-induced EMT through cancer-stromal interactions in endometrial cancer.

Peroxisome proliferator-activated receptor-γ coactivator 1α-mediated pathway as a possible therapeutic target in endometriosis.

STUDY QUESTION: Is a peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)-mediated pathway involved in the development of endometriosis? SUMMARY ANSWER: PGC-1α plays critical roles in inflammation and cell proliferation of endometriotic tissues and may be involved in the development of endometriosis. WHAT IS KNOWN ALREADY: Expression levels of PGC-1α are higher in ovarian endometrioma (OE) than normal endometrium (NE). PGC-1α also stimulates aromatase activity and promotes local estrogen biosynthesis in OE. STUDY DESIGN, SIZE, DURATION: This is a case-controlled biological study using endometrial cells and tissues derived from 23 women with, and 10 women without, OE. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ectopic endometriotic and eutopic endometrial stromal cells (SCs) were isolated and maintained in culture. PGC-1α was either overexpressed in the cells or knocked down using siRNA. The expression of PGC-1α and other factors during endometriosis was examined using real-time PCR and western blotting, cell proliferation was measured using Cell Counting Kit-8 (WST-8) assays and transcriptional activity was assessed using luciferase reporter assays. MAIN RESULTS AND THE ROLE OF CHANCE: PGC-1α overexpression promoted the proliferation of OESCs in a time-dependent manner (P < 0.01 versus control) but not NESCs. PGC-1α stimulated aromatase (P < 0.01 versus control) and interleukin (IL)-6/IL-8 mRNA expression levels (P < 0.05 versus control for each) and led to inhibitor kappa B phosphorylation protein expression and upregulation of the apoptosis inhibitors X-linked inhibitor of apoptosis protein and survivin at mRNA level (P < 0.05 versus control for each). HX531, a selective retinoid-X receptor-α (RXRα) antagonist, suppressed the PGC-1α-induced cell proliferation (P < 0.05 versus control), aromatase/IL-6/IL-8/survivin mRNA expression (P < 0.05 versus control for each) and transcription reporter activity of PGC-1α in a dose-dependent manner (P < 0.01 versus control). Moreover, HX531 downregulated PGC-1α-induced aromatase-promoter PI.3-II transcripts in OESCs, and PGC-1α knockdown reduced aromatase, IL-6/IL-8 and antiapoptotic factors mRNA expression (P < 0.05 versus control for each). Notably, the Histogram score, which was used for quantifying RXRα status, was markedly higher in OE than in NE tissue (P < 0.01). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Only OE tissues were included in this study, while peritoneal and deep infiltrating endometriotic tissues were not. Therefore, these findings might not be generalized to other types of endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: In OESC, PGC-1α stimulated cell proliferation and was involved in local estrogen biosynthesis, inflammation and apoptosis, and these effects of PGC-1α were inhibited by HX531. The suppression of PGC-1α-induced proliferation by HX531 in OESCs but not NESCs suggests that the PGC-1α-RXRα axis could play critical roles in promoting endometriosis. This is the first report of a relationship between PGC-1α and inhibitor of apoptosis proteins in endometriosis. Based on these findings, the PGC-1α-mediated pathway could represent a potential target in molecular therapy of endometriosis. STUDY FUNDING/COMPETING INTEREST(S): The study is supported in part by Grants-in-Aid for Scientific Research (15 K10681 and 15 K10726) from the Ministry of Education, Culture, Sports, Science, and Technology (Japan). The authors have no conflicts of interest to disclose.

Antitumor effect of XCT790, an ERRα inverse agonist, on ERα-negative endometrial cancer cells.

PURPOSE: The estrogen-related receptor (ERR) α is structurally similar to classical estrogen receptors (ERs), but is considered to be an orphan nuclear receptor. We previously found that ERRα regulates uterine endometrial cancer progression. Here, we investigated the efficacy of XCT790, a selective inverse agonist of ERRα, on endometrial cancer cells in vitro and in vivo. METHODS: HEC-1A and KLE, ERα-negative endometrial cancer cells exhibiting high ERRα expression levels, and HEC-1A cell-derived xenograft model mice were treated with XCT790. Transcriptional activity and cell proliferation were examined using luciferase, WST-8 and colony formation assays, respectively. Cell cycle progression was evaluated using flow cytometry, immunofluorescence cytochemistry and Western blotting. Apoptosis was evaluated using a caspase-3/7 activity assay. RESULTS: We found that XCT790 significantly inhibited ERRα-induced in vitro transcriptional activity, including that of the vascular endothelial growth factor (VEGF) gene, in a concentration-dependent manner (p < 0.05). We also found that XCT790 suppressed colony formation and cell proliferation in a concentration and time-dependent manner (p < 0.01) without cytotoxicity, and induced apoptosis (p < 0.01). XCT790 was found to cause cell cycle arrest at the mitotic phase. Akt and mTOR phosphorylation was found to be inhibited by XCT790, but PI3K levels were not found to be significantly affected. Combination therapy of XCT790 with paclitaxel elicited a synergistic inhibitory effect. Additionally, we found that XCT790 significantly inhibited in vivo tumor growth and angiogenesis, and induced apoptosis without a reduction in body weight, in xenograft models (p < 0.01). CONCLUSIONS: From our data we conclude that XCT790 has an anti-tumor effect on endometrial cancer cells in vitro and in vivo. As such, it may serve as a novel therapeutic agent for endometrial cancer.

Equilin in conjugated equine estrogen increases monocyte-endothelial adhesion via NF-κB signaling.

The adhesion of monocytes to endothelial cells, which is mediated by adhesion molecules, plays a crucial role in the onset of atherosclerosis. Conjugated equine estrogen, which is widely used for estrogen-replacement therapy, contains both estrone sulfate and various nonhuman estrogens, including equilin. To investigate the association between various estrogen types and atherosclerosis risk, we examined their effect on adhesion-molecule expression in human umbilical vein endothelial cells (HUVECs). In estrogen-treated HUVECs, the mRNA and protein expression levels of adhesion molecules were quantified by real-time polymerase chain reaction and enzyme immunoassay. Additionally, a flow-chamber system was used to assess the effects of estrogens on the adherence of U937 monocytoid cells to HUVECs. Equilin, but not 17ß-estradiol (E2) or other types of estrogen, significantly increased the mRNA (P < 0.01) and protein (P < 0.05) expression of the adhesion molecules E-selectin and intercellular adhesion molecule-1 as compared with levels in controls. Equilin treatment increased the adherence of U937 monocytoid cells to HUVECs relative to the that in the control (P < 0.05), decreased estrogen receptor (ER)ß expression, and increased the expression of proteins involved in nuclear factor kappa-B (NF-κB) activation relative to levels in controls. Furthermore, the accumulation of NF-κB subunit p65 in HUVEC nuclei was promoted by equilin treatment. By contrast, E2 treatment neither increased the number of adhered monocytoid cells to HUVECs nor altered the expression of ERß or NF-κB-activating proteins. Our findings suggest that in terms of the adhesion of monocytes at the onset of atherosclerosis, E2 may be preferable for estrogen-replacement therapy. Further studies comparing equilin treatment with that of E2 are needed to investigate their differential impacts on atherosclerosis.

Long-term survival with bevacizumab in heavily pretreated and platinum-resistant mucinous ovarian cancer: A case report.

The prognosis of patients with recurrent and platinum-resistant ovarian cancer is quite poor. Randomized trials have shown that bevacizumab (BEV) can be effective, even in platinum-resistant ovarian cancer, but only a few such cases of long-term survival with BEV have been reported. Furthermore, there is no consensus on how many cycles of BEV should be administered. Herein, we report a case of refractory mucinous ovarian cancer showing long-term survival after six cycles of weekly paclitaxel with BEV followed by 26 cycles of BEV maintenance. Although six prior chemotherapy regimens resulted in progressive disease, the BEV treatment controlled the patient's ascites and improved her performance status. For a further 30 months and 32 cycles of BEV, neither progression of the disease nor severe adverse events have been observed. Our case demonstrates that BEV administration could result in a favorable outcome in heavily pretreated and platinum-resistant ovarian cancer patients.

Endometrioid adenocarcinoma arising from deep infiltrating endometriosis involving the bladder: A case report and review of the literature.

•Malignant transformation of deep infiltrating endometriosis involving the bladder is quite rare.•We review eight relevant cases which have been reported.•This is the second case fulfilling Sampson and Scott criteria.