- Comparison of routine pelvic US and MR imaging in patients with pathologically confirmed endometriosis. [Journal Article]
- ARAbdom Radiol (NY) 2019 Jul 12
- CONCLUSIONS: Pelvic MR imaging had a higher detection rate of surgically/pathologically proven endometriosis and provides more information about disease location and sequela compared to routine pelvic US.
- Association between the cervicovaginal microbiome, BRCA1 mutation status, and risk of ovarian cancer: a case-control study. [Journal Article]
- LOLancet Oncol 2019 Jul 09
- CONCLUSIONS: The presence of ovarian cancer, or factors known to affect risk for the disease (ie, age and BRCA1 germline mutations), were significantly associated with having a community type O cervicovaginal microbiota. Whether re-instatement of a community type L microbiome by using, for example, vaginal suppositories containing live lactobacilli, would alter the microbiomial composition higher up in the female genital tract and in the fallopian tubes (the site of origin of high-grade serous ovarian cancer), and whether such changes could translate into a reduced incidence of ovarian cancer, needs to be investigated.
- Proteomic analysis reveals a role for PAX8 in peritoneal colonization of high grade serous ovarian cancer that can be targeted with micelle encapsulated thiostrepton. [Journal Article]
- OOncogene 2019 Jul 11
- High grade serous ovarian cancer (HGSOC) is the fifth leading cause of cancer deaths among women yet effective targeted therapies against this disease are limited. The heterogeneity of HGSOC, includi…
High grade serous ovarian cancer (HGSOC) is the fifth leading cause of cancer deaths among women yet effective targeted therapies against this disease are limited. The heterogeneity of HGSOC, including few shared oncogenic drivers and origination from both the fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE), has hampered development of targeted drug therapies. PAX8 is a lineage-specific transcription factor expressed in the FTE that is also ubiquitously expressed in HGSOC where it is an important driver of proliferation, migration, and cell survival. PAX8 is not normally expressed in the OSE, but it is turned on after malignant transformation. In this study, we use proteomic and transcriptomic analysis to examine the role of PAX8 leading to increased migratory capabilities in a human ovarian cancer model, as well as in tumor models derived from the OSE and FTE. We find that PAX8 is a master regulator of migration with unique downstream transcriptional targets that are dependent on the cell's site of origin. Importantly, we show that targeting PAX8, either through CRISPR genomic alteration or through drug treatment with micelle encapsulated thiostrepton, leads to a reduction in tumor burden. These findings suggest PAX8 is a unifying protein driving metastasis in ovarian tumors that could be developed as an effective drug target to treat HGSOC derived from both the OSE and FTE.
- Investigation and management of subfertility. [Review]
- JCJ Clin Pathol 2019 Jul 11
- Subfertility affects one in seven couples and is defined as the inability to conceive after 1 year of regular unprotected intercourse. This article describes the initial clinical evaluation and inves…
Subfertility affects one in seven couples and is defined as the inability to conceive after 1 year of regular unprotected intercourse. This article describes the initial clinical evaluation and investigation to guide diagnosis and management. The primary assessment of subfertility is to establish the presence of ovulation, normal uterine cavity and patent fallopian tubes in women, and normal semen parameters in men. Ovulation is supported by a history of regular menstrual cycles (21-35 days) and confirmed by a serum progesterone >30 nmol/L during the luteal phase of the menstrual cycle. Common causes of anovulation include polycystic ovary syndrome (PCOS), hypothalamic amenorrhoea (HA) and premature ovarian insufficiency (POI). Tubal patency is assessed by hysterosalpingography, hystero-contrast sonography, or more invasively by laparoscopy and dye test. The presence of clinical or biochemical hyperandrogenism, serum gonadotrophins (luteinising hormone/follicle stimulating hormone) / oestradiol, pelvic ultrasound to assess ovarian morphology / antral follicle count, can help establish the cause of anovulation. Ovulation can be restored in women with PCOS using letrozole (an aromatase inhibitor), clomifene citrate (an oestrogen antagonist) or exogenous gonadotrophin administration. If available, pulsatile gonadotrophin releasing hormone therapy is the preferred option for restoring ovulation in HA. Spermatogenesis can be induced in men with hypogonadotrophic hypogonadism with exogenous gonadotrophins. Unexplained subfertility can be treated with in vitro fertilisation after 2 years of trying to conceive. Involuntary childlessness is associated with significant psychological morbidity; hence, expert assessment and prompt treatment are necessary to support such couples.
- Ectopic pregnancy in left ovary and contralateral uterine tube diagnosed one week apart in In Vitro Fertilization with donor eggs: Case report. [Case Reports]
- JAJBRA Assist Reprod 2019 Jul 11
- Bilateral ectopic pregnancy is a rare clinical condition with an estimated prevalence of 1/200 000 in spontaneous pregnancies. Studies have found that In Vitro Fertilization (IVF) is related to ectop…
Bilateral ectopic pregnancy is a rare clinical condition with an estimated prevalence of 1/200 000 in spontaneous pregnancies. Studies have found that In Vitro Fertilization (IVF) is related to ectopic pregnancy independently, but the incidence of tubal disease in the donor egg recipient population is thought to be significantly lower than in the standard IVF population. We report the case of a patient participating in the egg-sharing program, who was diagnosed with ovarian ectopic pregnancy, treated with surgery. After one week, she was diagnosed with tubal ectopic pregnancy in the contralateral tube. The clinician should be aware that the treatment of one ectopic pregnancy does not preclude the occurrence of a second ectopic pregnancy in the same patient and should pay attention to the intra-operatory inspection of both side fallopian tubes in any ectopic pregnancy case. Routine ultrasound after ectopic pregnancy treatment may be reasonable, especially in high risk patients.
- A Case of Mixed Gonadal Dysgensis: A Diagnostic Challenge. [Case Reports]
- JHJ Hum Reprod Sci 2019 Apr-Jun; 12(2):169-172
- A 2-year-old child reared as a girl child was brought by parents with ambiguous genitalia noticed since birth. There was no history of failure to thrive or salt-losing crisis. On examination, the chi…
A 2-year-old child reared as a girl child was brought by parents with ambiguous genitalia noticed since birth. There was no history of failure to thrive or salt-losing crisis. On examination, the child had normal height and weight with normal blood pressure and no dysmorphism or Turners stigmata with external genitalia Prader Score 2. Ultrasound of the pelvis revealed hypoplastic uterus with no gonads visualized. There was no evidence of hypocortisolemia (8 am cortisol 14.08 mcg/dl) or elevated level of 17-OH-progesterone (1.1 ng/mL). Pooled follicle-stimulating hormone and luteinizing hormone levels were 2.66 mIU/ml and 0.1 mIU/ml, respectively, thyroid-stimulating hormone: 2.36 mIU/L, T4: 134.5 nmol/L, total testosterone: 2.5 ng/dl. Posthuman chorionic gonadotropin stimulation showed total testosterone levels 267 ng/dL, dihydrotestosterone: 155 pg/mL, androstenedione: 0.3 ng/mL indicating functioning testicular tissue without any evidence of 17-beta hydroxylase or 5-alpha reductase deficiency. Karyotyping revealed 45, XO genotype on two separate occasions. In view of the discrepancy between karyotype finding and ultrasound reports with the clinical and hormonal picture, fluorescence in situ hybridization cytogenetic study was carried out and showed MONOSOMY X (90% cells)/SEX ANEUPLOIDY XYY (10% cells). Laparoscopic examination showed gonad in the right ovarian fossa and left streak gonad with bilateral fallopian tubes and hypoplastic uterus. Genitoscopy showed normal vagina and cervix. Cystoscopy showed normal urethra and urinary bladder. Biopsy was taken from both gonads. A thorough histopathological examination of this specimen showed the structure of seminiferous tubules with Leydig cells in the right gonad with streak ovary on the left side. The child underwent bilateral gonadectomy and rehabilitated her to lead a life as a girl.
- BORIS expression in ovarian cancer precursor cells alters the CTCF cistrome and enhances invasiveness through GALNT14. [Journal Article]
- MCMol Cancer Res 2019 Jul 10
- High-grade serous carcinoma (HGSC) is the most aggressive and predominant form of epithelial ovarian cancer and the leading cause of gynecological cancer death. We have previously shown that CTCFL (a…
High-grade serous carcinoma (HGSC) is the most aggressive and predominant form of epithelial ovarian cancer and the leading cause of gynecological cancer death. We have previously shown that CTCFL (also known as BORIS, Brother of the Regulator of Imprinted Sites) is expressed in most ovarian cancers, and is associated with global and promoter-specific DNA hypomethylation, advanced tumor stage, and poor prognosis. To explore its role in HGSC, we expressed BORIS in human fallopian tube secretory epithelial cells (FTSEC), the presumptive cells of origin for HGSC. BORIS-expressing cells exhibited increased motility and invasion, and BORIS expression was associated with alterations in several cancer-associated gene expression networks, including fatty acid metabolism, TNF signaling, cell migration, and ECM-receptor interactions. Importantly, GALNT14, a glycosyltransferase gene implicated in cancer cell migration and invasion, was highly induced by BORIS, and GALNT14 knockdown significantly abrogated BORIS-induced cell motility and invasion. In addition, in silico analyses provided evidence for BORIS and GALNT14 co-expression in several cancers. Finally, ChIP-seq demonstrated that expression of BORIS was associated with de novo and enhanced binding of CTCF at hundreds of loci, many of which correlated with activation of transcription at target genes, including GALNT14. Taken together, our data indicate that BORIS may promote cell motility and invasion in HGSC via upregulation of GALNT14, and suggests BORIS as a potential therapeutic target in this malignancy. Implications: These studies provide evidence that aberrant expression of BORIS may play a role in the progression to HGSC by enhancing the migratory and invasive properties of FTSEC.
- Expression levels of MRP1, GST-π, and GSK3β in ovarian cancer and the relationship with drug resistance and prognosis of patients. [Journal Article]
- OLOncol Lett 2019; 18(1):22-28
- Expression levels of multidrug resistance-associated protein 1 (MRP1), glutathione S-transferase π (GST-π) and glycogen synthase kinase-3β (GSK3β) were investigated in ovarian epithelial cancer and t…
Expression levels of multidrug resistance-associated protein 1 (MRP1), glutathione S-transferase π (GST-π) and glycogen synthase kinase-3β (GSK3β) were investigated in ovarian epithelial cancer and the relationship with the primary drug resistance of patients with ovarian cancer to chemotherapy. One hundred and twenty-one ovarian cancer tissue samples from patients who underwent ovarian cancer resection from January 2013 to June 2015 in Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University were enrolled in the Experimental group, while 58 ovarian tissue samples from patients with fallopian tube obstruction but with no ovarian cancer who received surgical treatment for blocked fallopian tube were included in the Control group. After the detection of the expression levels of MRP1, GST-π, and GSK3β mRNA by RT-PCR and the analysis of related clinical pathological factors, patients in the Experimental group were divided into the Chemotherapy-sensitive and Chemotherapy-resistant groups according to the chemotherapy efficacy. Additionally, with the mean expression levels of MRP1, GST-π, and GSK3β in ovarian cancer tissues as the boundaries, the expression levels of the three genes in the Experimental group were classified into high expression and low expression. Ovarian cancer tissues had much higher expression levels of MRP1, GST-π, and GSK3β mRNA than normal ovarian tissues (P<0.05). The expression levels of MRP1, GST-π, and GSK3β mRNA in the Chemotherapy-sensitive group were significantly lower than those in the Chemotherapy-resistant group (P<0.05). Patients with high expression of MRP1, GST-π, and GSK3β mRNA had a much lower 3-year survival rate than patients with low expression of the genes (P<0.05). Highly expressed in patients with ovarian cancer, MRP1, GST-π, and GSK3β mRNA play an important role in the development and drug resistance of ovarian cancer, which ensures this study is of positive clinical guiding significance in developing proper treatment for ovarian cancer and evaluating the efficacy of chemotherapy.
- Salpingectomy at the time of hysterectomy for benign gynaecological disease: A comparison of surgical approaches. [Journal Article]
- ANAust N Z J Obstet Gynaecol 2019 Jul 08
- Given that a significant percentage of high-grade serous cancers develop in the fallopian tube, it has been suggested that salpingectomy may prevent some of these malignancies. The Royal Australian a…
Given that a significant percentage of high-grade serous cancers develop in the fallopian tube, it has been suggested that salpingectomy may prevent some of these malignancies. The Royal Australian and New Zealand College of Obstetricians and Gynaecologists guidelines recommend prophylactic salpingectomy to be discussed with or offered to patients undergoing hysterectomy for benign indications. This study compares rates of salpingectomy at the time of hysterectomy for benign indications across different surgical approaches among Australian and New Zealand gynaecologists. Data were collected via SurgicalPerformance, a web-based surgical outcomes review and feedback software used by independent gynaecologic surgeons. Of 11 477 hysterectomy records available, 6608 were eligible for analysis. Rates of salpingectomy at vaginal hysterectomy (13%) were significantly lower (P < 0.001) compared to open abdominal (65%), laparoscopic (70%), laparoscopic-assisted vaginal (78%), or robotic hysterectomies (73%) and also lower than in hysterectomies converted to an open abdominal approach (73%).
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- Influence of a mannose-binding lectin gene polymorphism and exposure to Chlamydia trachomatis on fallopian tube obstruction in Brazilian woman. [Journal Article]
- AGArch Gynecol Obstet 2019 Jul 08
- CONCLUSIONS: The level of MBL-related innate immunity influences the consequences of infection by C. trachomatis or other microbes.