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- The differential expression of microRNA-143,145 in endometriosis. [JOURNAL ARTICLE]
- Iran J Reprod Med 2014 Aug; 12(8):555-560.
Background: Recent studies showed that inappropriate expression of microRNAs (miRNAs) is strongly associated with tumor-related processes in humans (2-9,11-17). Objective: To understand the changes of miRNAs in endometriosis. Materials and Methods: With real-time RT-PCR, we investigated the miR-143 and miR-145 expression in eutopic (EU, n=2) and ectopic endometrium (EC, n=11) (from women with endometriosis) (as well as EU+EC, n=11), along with the normal endometrium (EN, n=22) (from women without endometriosis, but with leiomyoma). Results: We did not find that the expression of miR-143 and/or miR-145 in EN or EC changed with menstrual cycle. But our results showed the miR-143 was up-regulated in EC (p=0.000) compared to EN. The miR-143 was also up-regulated in EU, but the difference did not reach statistically significance (p=0.053). Compared to EU, the expression of miR-143 in EC was up-regulated (p=0.016). MiR-145 had the similar characteristic to miR-143. The miR-145 was up-regulated in both EU (p=0.004) and EC (p=0.000) in compared to EN group. When compared with EU, the miR-145 in EC was up-regulated (p=0.008). Conclusion: In conclusion, the miR-143 and miR-145 may play a certain role in the development and progression of endometriosis.
- Role of nuclear progesterone receptor isoforms in uterine pathophysiology. [REVIEW]
- Hum Reprod Update 2014 Nov 18.
Progesterone is a key hormonal regulator of the female reproductive system. It plays a major role to prepare the uterus for implantation and in the establishment and maintenance of pregnancy. Actions of progesterone on the uterine tissues (endometrium, myometrium and cervix) are mediated by the combined effects of two progesterone receptor (PR) isoforms, designated PR-A and PR-B. Both receptors function primarily as ligand-activated transcription factors. Progesterone action on the uterine tissues is qualitatively and quantitatively determined by the relative levels and transcriptional activities of PR-A and PR-B. The transcriptional activity of the PR isoforms is affected by specific transcriptional coregulators and by PR post-translational modifications that affect gene promoter targeting. In this context, appropriate temporal and cell-specific expression and function of PR-A and PR-B are critical for normal uterine function.Relevant studies describing the role of PRs in uterine physiology and pathology (endometriosis, uterine leiomyoma, endometrial cancer, cervical cancer and recurrent pregnancy loss) were comprehensively searched using PubMed, Cochrane Library, Web of Science, and Google Scholar and critically reviewed.Progesterone, acting through PR-A and PR-B, regulates the development and function of the endometrium and induces changes in cells essential for implantation and the establishment and maintenance of pregnancy. During pregnancy, progesterone via the PRs promotes myometrial relaxation and cervical closure. Withdrawal of PR-mediated progesterone signaling triggers menstruation and parturition. PR-mediated progesterone signaling is anti-mitogenic in endometrial epithelial cells, and as such, mitigates the tropic effects of estrogen on eutopic normal endometrium, and on ectopic implants in endometriosis. Similarly, ligand-activated PRs function as tumor suppressors in endometrial cancer cells through inhibition of key cellular signaling pathways required for growth. In contrast, progesterone via PR activation appears to increase leiomyoma growth. The exact role of PRs in cervical cancer is unclear. PRs regulate implantation and therefore aberrant PR function may be implicated in recurrent pregnancy loss (RPL). PRs likely regulate key immunogenic factors involved in RPL. However, the exact role of PRs in the pathophysiology of RPL and the use of progesterone for therapeutic benefit remains uncertain.PRs are key mediators of progesterone action in uterine tissues and are essential for normal uterine function. Aberrant PR function (due to abnormal expression and/or function) is a major cause of uterine pathophysiology. Further investigation of the underlying mechanisms of PR isoform action in the uterus is required, as this knowledge will afford the opportunity to create progestin/PR-based therapeutics to treat various uterine pathologies.
- Leiomyoma of female urethra. [Journal Article]
- J Obstet Gynaecol India 2014 Dec; 64(Suppl 1):138-9.
- Pulmonary benign metastasizing leiomyoma: a case report. [Journal Article]
- Int J Clin Exp Pathol 2014; 7(10):7072-5.
Pulmonary benign metastasizing leiomyoma (PBML) is a rare entity usually occurring in females with history of uterine leiomyoma, and it is preferential to metastasize to the lung and appears as a histopathologic benign tumor of smooth muscle origin. In this article, the clinical and pathological data from 1 patient with PBML were analyzed. Chest CT scan showed that multiple well-defined nodules in the both lobes of the lungs. The tumor cells in the lung were well differentiated, and the pattern of tumor was similar to the original tumor. IHC identified it originated from smooth muscle cells, consistent with the diagnosis of PBML. Positive staining of estrogen and progestogen receptors was detected in both the leiomyoma and the metastasizing lesions. During two years of observation, pulmonary function parameters were within normal limits and there was no evidence of tumor recurrence.
- Preoperative diagnosis of usual leiomyoma, atypical leiomyoma, and leiomyosarcoma. [Journal Article]
- Sarcoma 2014.:498682.
Uterine smooth muscle tumors (SMTs) are common pelvic tumors in women, and most of them are diagnosed as usual leiomyoma (UL). Exclusion of malignant disease is important in the management of SMTs. However, differentiation of SMTs remains difficult. In this study, we aimed to improve the preoperative diagnosis of SMTs. We examined 21 ULs, 7 atypical leiomyomas (ALs), and 6 leiomyosarcomas (LMSs), all of which were diagnosed by uterine tumor biopsy. Immunohistochemical findings (low-molecular-mass polypeptide 2 (LMP2) and Ki-67) and clinical features (serum lactate dehydrogenase level and menopause) were evaluated. Statistically significant differences in the expression of LMP2 and Ki-67 were observed between UL and AL and between UL and LMS. The combined LMP2 and Ki-67 score was significantly different between UL and AL, between UL and LMS, and between AL and LMS. The combined immunohistochemistry and clinical findings score (total score) was also significantly different between pathological types. The findings of this study suggest that the accuracy of the preoperative diagnosis of SMTs may be improved by using a combination of immunohistochemical and clinical findings.
- Differential effects of tumor necrosis factor-α on matrix metalloproteinase-2 expression in human myometrial and uterine leiomyoma smooth muscle cells. [JOURNAL ARTICLE]
- Hum Reprod 2014 Nov 14.
Does tumor necrosis factor-α (TNF-α) differentially regulate matrix metalloproteinase-2 (MMP-2) expression in leiomyomas compared with normal myometrium?TNF-α up-regulates MMP-2 expression and stimulates cell migration through the activation of extracellular signal-regulated kinase (ERK) signaling pathway in leiomyoma smooth muscle cells (SMCs), but not in normal myometrial SMCs.Uterine leiomyoma, the benign smooth muscle cell tumor, is the single most common indication for hysterectomy. High expression of MMPs or TNF-α has been reported in uterine leiomyomas; however, the molecular mechanism underlying these observations remains unknown.Samples were obtained between 2009 and 2013 from 12 women of reproductive age at the proliferative phase of the menstrual cycle by hysterectomy. Leiomyomas and matched normal myometrium from each woman were analyzed in vitro.Western blot, RT-qPCR and a wound-healing assay were used to investigate the effects of TNF-α on MMP-2 expression and intracellular signal transduction in cultured SMCs from leiomyomas and matched myometrium.Western blot and RT-qPCR analyses using tissues from clinical patients showed that the levels of MMP-2 protein (P = 0.008) and mRNA (P = 0.009) were significantly higher in uterine leiomyomas compared with their matched myometrium. Treatment with TNF-α significantly up-regulated the protein (P = 0.039) and mRNA (P = 0.037) levels of MMP-2 in cultured leiomyoma SMCs but not in matched myometrial SMCs. The extracellular signal-regulated kinase (ERK) and nuclear factor-kappa B (NF-κB) pathways were activated by TNF-α in leiomyoma SMCs. Specific inhibitors of the ERK or NF-κB pathway (PD98059 or Bay11-7082) suppressed TNF-α-induced MMP-2 expression in leiomyoma SMCs. The wound-healing assay revealed that TNF-α promoted the migration of cultured leiomyoma SMCs (P = 0.036); however, PD98059 compromised the cell migration triggered by TNF-α.This study is descriptive and although we observed clear differential regulation of MMP-2 by TNF-α at mRNA and protein levels in leiomyoma, future studies are needed to identify why the difference in TNF-α response exists between human leiomyoma tissue and normal myometrium. Including some of the experiments such as transfection studies for TNF-α and MMP-2 promoter mapping could have added more insight as to why this difference exists. In addition, further studies in vivo are needed to verify the results obtained from primary cultured SMCs.Considering the positive effect of TNF-α on leiomyoma SMC migration, strategies targeting TNF-α, in parallel with the production of more speciﬁc inhibitors of MMPs, may provide alternative therapeutic approaches for the treatment of leiomyoma.This work was partially supported by grants from the Program for New Century Excellent Talents in University (NCET-12-0282), National Natural Science Foundation of China (81371620) and Tianjin Natural Science Foundation (12JCZDJC24900). The authors have no conflicts of interest to declare.
- Extrauterine fibroids: a diagnostic challenge and a long-term battle. [Journal Article]
- BMJ Case Rep 2014.
Extrauterine fibroids often present a diagnostic challenge due to the unusual locations they arise from. We present a series of rare extrauterine fibroids. In recent years, these fibroids have been associated with previous morcellated hysterectomies or myomectomies. Our series of six patients were found to have extrauterine fibroids (confirmed through histology) and underwent open hysterectomy and open or laparoscopic myomectomy. Four had undergone previous laparoscopic myomectomies while the other two had no previous intra-abdominal surgeries. Postsurgical occurrence may be caused by incomplete removal of morcellated fibroid tissue. Spontaneous occurrence can be associated with congenital Müllerian system defects. Extrapolating from this hypothesis, we recommend physicians to make sure that counselling for extrauterine seeding and dissemination of unexpected malignancy is undertaken in cases of minimally invasive surgeries where morcellation is expected. Long-term tumour surveillance is thus essential in such instances.
- [Inflammation, malignancy and immunology in gastrointestinal spindle cell tumors : What is beyond GIST?]. [English Abstract, Journal Article]
- Pathologe 2014 Nov.:207-13.
Many mesenchymal tumors and tumefactions associated with the gastrointestinal tract feature prominent inflammatory cells but the mechanisms for the inflammation and the processes themselves remain poorly understood. Such classic lesions include Kaposi sarcoma, inflammatory fibroid polyp, sclerosing mesenteritis and inflammatory myofibroblastic tumor but, more recently, the recognition of IgG4-related fibrosclerosing disease has resulted in modification of the views on pathogenesis and treatment of such inflammatory lesions in many anatomical sites. In some lesions the inflammation may reflect viral influences (Kaposi sarcoma) or a bacterial infectious trigger (IgG4-related fibrosclerosing disease) whereas in others such an interaction is unclear and alterations in various genes have been detected, such as anaplastic lymphoma receptor tyrosine kinase gene rearrangements in inflammatory myofibroblastic tumor and platelet-derived growth factor receptor alpha (PDGFRA) gene mutations in inflammatory fibroid polyp and some gastrointestinal stromal tumors (GIST). Even the inflammatory milieu of GISTs may have an impact on the outcome. This article discusses the practical diagnostic considerations as well as the theoretical background.
- Pregnancy outcomes after myomectomy with polytetrafluoroethylene placement. [Journal Article]
- JSLS 2014 Jul; 18(3)
The aim of this study was to report preliminary data on pregnancy outcomes after myomectomy with placement of an expanded polytetrafluoroethylene adhesion barrier membrane.In this retrospective case series, 68 women who underwent myomectomy with expanded polytetrafluoroethylene membrane placement between January 1, 2003, and December 31, 2009, were identified. Of these women, 15 subsequently had documented pregnancies and were included in the final dataset.Eighteen pregnancies were documented among 15 women. There were no reported cases of preterm labor, preterm premature rupture of membranes, or uterine rupture.In this case series, there were no documented cases of preterm labor, preterm premature rupture of membranes, or uterine rupture after myomectomy with expanded polytetrafluoroethylene membrane placement.