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Genomic and proteomic profiling II: Comparative assessment of gene expression profiles in leiomyomas, keloids, and surgically-induced scars
Xiaoping Luo, Qun Pan, Li Liu, Nasser Chegini
Reproductive Biology and Endocrinology , 2007, DOI: 10.1186/1477-7827-5-35
Abstract: Microarray gene expression profiling and realtime PCR.The analysis identified 3 to 12% of the genes on the arrays as differentially expressed among these tissues based on P ranking at greater than or equal to 0.005 followed by 2-fold cutoff change selection. Of these genes about 400 genes were identified as differentially expressed in leiomyomas as compared to keloids/incisional scars, and 85 genes as compared to peritoneal adhesions (greater than or equal to 0.01). Functional analysis indicated that the majority of these genes serve as regulators of cell growth (cell cycle/apoptosis), tissue turnover, transcription factors and signal transduction. Of these genes the expression of E2F1, RUNX3, EGR3, TBPIP, ECM-2, ESM1, THBS1, GAS1, ADAM17, CST6, FBLN5, and COL18A was confirmed in these tissues using quantitative realtime PCR based on low-density arrays.the results indicated that the molecular feature of leiomyomas is comparable but may be under different tissue-specific regulatory control to those of keloids and differ at the levels rather than tissue-specific expression of selected number of genes functionally regulating cell growth and apoptosis, inflammation, angiogenesis and tissue turnover.Leiomyomas are benign uterine tumors with unknown etiology that originate from transformation of myometrial smooth muscle cells and/or connective tissue fibroblasts during the reproductive years. Leiomyomas can develop in multiple numbers that are individually encapsulated by a connective tissue core separating them from the surrounding normal myometrium and are ovarian steroid-dependent for their growth. Although they occur independent of ethnicity, clinical and epidemiological studies have indicated that African Americans are at a higher risk of developing leiomyomas compared to other ethnic groups [1].Leiomyomas have also often been compared to keloids because of a higher rate of occurrence in African Americans and their fibrotic characteristics despite differences in the
Experimental model of the formation of pelvic adhesions by videolaparoscopic in female rabbits
Balbinotto, Rosi Pereira;Trindade, Manoel Roberto Maciel;Muller, Ana Lucia Letti;Nunes, André Gorgen;Silva, Rodrigo Da;Meyer, Fabíola Schons;Cerski, Carlos Thadeu Schmidt;
Acta Cirurgica Brasileira , 2010, DOI: 10.1590/S0102-86502010000100009
Abstract: purpose: to verify the frequency of postsurgical pelvic adhesion formation in an experimental animal model using videolaparoscopy. methods: experimental study in a sample of 11 non-pregnant female rabbits, aged 5 to 7 months. after general anesthesia, access to the abdominal cavity was performed by an open puncture technique, with 10mm optics, placing two other 5 mm trochars under direct visualization, in the iliac fossae. then a fragment of peritoneum was resected, followed by electrocauterization. in 21 days, the videolaparoscopy was repeated, and adhesion formation and score was looked at, with biopsies at the surgical site. results: 54 % of adhesion formation was observed, and the median score of adhesions was 6 (minimum of 3 and maximum of 10), all of them found in the bladder and the anterior abdominal wall. conclusion: the method used presents a high frequency of intra-abdominal adhesion formation.
Profiling and Functional Analyses of MicroRNAs and Their Target Gene Products in Human Uterine Leiomyomas  [PDF]
Jiri Zavadil,Huihui Ye,Zhaojian Liu,JingJing Wu,Peng Lee,Eva Hernando,Patricia Soteropoulos,Gokce A. Toruner,Jian-Jun Wei
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012362
Abstract: Human uterine leiomyomas (ULM) are characterized by dysregulation of a large number of genes and non-coding regulatory microRNAs. In order to identify microRNA::mRNA associations relevant to ULM pathogenesis, we examined global correlation patterns between the altered microRNA expression and the predicted target genes in ULMs and matched myometria.
Genomic and proteomic profiling I: Leiomyomas in African Americans and Caucasians
Qun Pan, Xiaoping Luo, Nasser Chegini
Reproductive Biology and Endocrinology , 2007, DOI: 10.1186/1477-7827-5-34
Abstract: Microarray, realtime PCR, 2D-PAGE, mass spectrometry, Western blotting and immunohistochemistry.Using Affymetrix U133A array and analysis based on P ranking (P < 0.01) 1470 genes were identified as differentially expressed in leiomyomas compared to myometrium regardless of ethnicity. Of these, 268 genes were either over-expressed (177 genes) or under-expressed (91 genes) based on P < 0.01 followed by 2-fold cutoff selection in leiomyomas of A. Americans as compared to Caucasians. Among them, the expression E2F1, RUNX3, EGR3, TBPIP, ECM2, ESM1, THBS1, GAS1, ADAM17, CST6, CST7, FBLN5, ICAM2, EDN1 and COL18 was validated using realtime PCR low-density arrays. 2D PAGE coupled with image analysis identified 332 protein spots of which the density/volume of 31 varied by greater than or equal to 1.5 fold in leiomyomas as compared to myometrium. The density/volume of 34 protein-spots varied by greater than or equal to 1.5 fold (26 increased and 8 decreased) in leiomyomas of A. Americans as compared to Caucasians. Tandem mass spectrometric analysis of 15 protein spots identified several proteins whose transcripts were also identified by microarray, including 14-3-3 beta and mimecan, whose expression was confirmed using western blotting and immunohistochemistry.These findings imply that the level rather than the ethnic-specific expression of a number of genes and proteins may account for the difference between leiomyomas and possibly myometrium, in A. Americans and Caucasians. Further study using larger sample size is required to confirm these findings.It has been estimated that 70% of women have a life-long risk of developing leiomyomas, with symptomatic tumors accounting for a 1/3 of all the hysterectomies preformed annually in the United States alone. Such estimates are even higher among African Americans with leiomyomas that develop earlier, become larger and more symptomatic as compared to other ethnic groups [1-3]. Since leiomyomas develop during the reproductive years a
Effectiveness of ovarian suspension in preventing post-operative ovarian adhesions in women with pelvic endometriosis: A randomised controlled trial
Wee-Liak Hoo, Ertan Saridogan, Alfred Cutner, George Pandis, Davor Jurkovic
BMC Women's Health , 2011, DOI: 10.1186/1472-6874-11-14
Abstract: A prospective double blind randomised controlled trial for patients with severe pelvic endometriosis requiring extensive laparoscopic dissection with preservation of the uterus and ovaries. Severity of the disease and eligibility for inclusion will be confirmed at surgery. Patients unable to provide written consent, inability to tolerate a transvaginal ultrasound scan, unsuccessful surgeries or suffer complications leading to oophorectomies, bowel injuries or open surgery will be excluded.Both ovaries are routinely suspended to the anterior abdominal wall during surgery. At the end of the operation, each participant will be randomised to having only one ovary suspended post-operatively. A new transabdominal suture will be reinserted to act as a placebo. Both sutures will be cut 36 to 48 hours after surgery before the woman is discharged home. Three months after surgery, all randomised patients will have a transvaginal ultrasound scan to assess for ovarian mobility. Both the patients and the person performing the scan will be blinded to the randomisation process.The primary outcome is the prevalence of ovarian adhesions on ultrasound examination. Secondary outcomes are the presence, intensity and site of post-operative pain.This controlled trial will provide evidence as to whether temporary ovarian suspension should be included into the routine surgical treatment of women with severe pelvic endometriosis.ISRCTN: ISRCTN24242218Endometriosis is a common benign condition, which is characterized by the growth of endometrium-like tissue in ectopic sites outside the uterus. The condition is a significant cause of morbidity in women of the reproductive age [1]. Symptoms of endometriosis include dysmenorrhoea, dyspareunia, chronic pelvic pain and subfertility. The revised American Society for Reproductive Medicine (ARSM) classification is the most widely accepted staging system for endometriosis, where a score is used to grade the disease as absent (0), minimal (1-5), mild (
ESOPHAGHEAL LEIOMYOMAS
E. Tarcoveanu,V. Strat,Felicia Crumpei,D. Ferariu
Jurnalul de Chirurgie , 2006,
Abstract: Esophageal leiomyomas, although infrequent, are the most common benign intramural tumors of the esophagus. They represent 10% of all gastro-intestinal leiomyomas and frequently cause symptoms, necessitating resection. We present two patients with esophageal leiomyoma which were treated one by enucleation and one by eso-gastric resection. None of the leiomyomas showed malignant transformation or recurrence. All symptomatic patients had relief of symptoms, with no perioperative morbidity or mortality.
Whole Exome Sequencing in a Random Sample of North American Women with Leiomyomas Identifies MED12 Mutations in Majority of Uterine Leiomyomas  [PDF]
Megan M. McGuire, Alexander Yatsenko, Lori Hoffner, Mirka Jones, Urvashi Surti, Aleksandar Rajkovic
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0033251
Abstract: Uterine leiomyomas (uterine fibroids) arise from smooth muscle tissue in the majority of women by age 45. It is common for these clonal tumors to develop from multiple locations within the uterus, leading to a variety of symptoms such as pelvic pain, abnormal uterine bleeding, and infertility. We performed whole exome sequencing on genomic DNA from five pairs of leiomyomas and corresponding normal myometrium to determine genetic variations unique to leiomyomas. Whole exome sequencing revealed that the gene encoding transcription factor MED12 (Mediator complex subunit 12) harbored heterozygous missense mutations caused by single nucleotide variants in highly conserved codon 44 of exon 2 in two of five leiomyomas. Sanger re-sequencing of MED12 among these five leiomyomas confirmed the two single nucleotide variants and detected a 42 base-pair deletion within exon 2 of MED12 in a third leiomyoma. MED12 was sequenced in an additional 143 leiomyomas and 73 normal myometrial tissues. Overall, MED12 was mutated in 100/148 (67%) of the genotyped leiomyomas: 79/148 (53%) leiomyomas exhibited heterozygous missense single nucleotide variants, 17/148 (11%) leiomyomas exhibited heterozygous in-frame deletions/insertion-deletions, 2/148 (1%) leiomyomas exhibited intronic heterozygous single nucleotide variants affecting splicing, and 2/148 (1%) leiomyomas exhibited heterozygous deletions/insertion-deletions spanning the intron 1-exon 2 boundary which affected the splice acceptor site. Mutations were not detected in MED12 in normal myometrial tissue. MED12 mutations were equally distributed among karyotypically normal and abnormal uterine leiomyomas and were identified in leiomyomas from both black and white American women. Our studies show an association between MED12 mutations and leiomyomas in ethnically and racially diverse American women.
Pathophysiology and prevention of postoperative peritoneal adhesions  [cached]
Willy Arung,Michel Meurisse,Olivier Detry
World Journal of Gastroenterology , 2011, DOI: 10.3748/wjg.v17.i41.4545
Abstract: Peritoneal adhesions represent an important clinical challenge in gastrointestinal surgery. Peritoneal adhesions are a consequence of peritoneal irritation by infection or surgical trauma, and may be considered as the pathological part of healing following any peritoneal injury, particularly due to abdominal surgery. The balance between fibrin deposition and degradation is critical in determining normal peritoneal healing or adhesion formation. Postoperative peritoneal adhesions are a major cause of morbidity resulting in multiple complications, many of which may manifest several years after the initial surgical procedure. In addition to acute small bowel obstruction, peritoneal adhesions may cause pelvic or abdominal pain, and infertility. In this paper, the authors reviewed the epidemiology, pathogenesis and various prevention strategies of adhesion formation, using Medline and PubMed search. Several preventive agents against postoperative peritoneal adhesions have been investigated. Their role aims in activating fibrinolysis, hampering coagulation, diminishing the inflammatory response, inhibiting collagen synthesis or creating a barrier between adjacent wound surfaces. Their results are encouraging but most of them are contradictory and achieved mostly in animal model. Until additional findings from future clinical researches, only a meticulous surgery can be recommended to reduce unnecessary morbidity and mortality rates from these untoward effects of surgery. In the current state of knowledge, pre-clinical or clinical studies are still necessary to evaluate the effectiveness of the several proposed prevention strategies of postoperative peritoneal adhesions.
Primary Fallopian Tube Carcinoma Arising in the Setting of Chronic Pelvic Inflammatory Disease  [PDF]
Ibrahim M. Zardawi
Case Reports in Medicine , 2014, DOI: 10.1155/2014/645045
Abstract: Primary fallopian tube cancer (PFTC) is a rare gynaecological malignancy, clinically often mistaken for pelvic inflammatory disease or ovarian cancer. Three primary fallopian tube carcinomas, arising in a background of chronic pelvic inflammatory disease (PID), are presented. The possible association between chronic PID and PFTC is discussed and a hypothesies linking these cancers with chronic inflammation is proposed. 1. Introduction Primary fallopian tube cancer (PFTC) is a relatively aggressive gynaecological malignancy. It accounts for 1% of all female genital malignancies [1–3]. The aetiology of PFTC is unknown but nulliparous women and women with germ-line BRCA mutation and women in certain occupations such as smelting workers, artistic workers, hairdressers, packers, nurses, shop workers, and clerical workers appear to be at increased risk of PFTC [4–7]. Serous papillary carcinoma is the most common histological type, accounting for >90% of the cases with these tumours. PID is very common and Chlamydia trachomatis infection is one of the most significant causes of chronic uterine tube inflammation [8]. Chlamydial infection has been associated with certain cancers [7, 9, 10]. This paper describes 3 cases of PFTC, clinically presenting as tuboovarian abscesses. A possible link between chronic PID and PFTC is suggested. 2. Materials and Methods Three cases of primary fallopian tube carcinomas, presenting between April 2011 and August 2013 with a clinical impression of an inflammatory tuboovarian mass, are described. Case 1 is a 46-year-old Indigenous woman, admitted in April 2011 with pelvic pain. Abdominal ultrasound showed a 130?mm complex left cystic adnexal mass which was clinically considered to be a tuboovarian abscess as there was a longstanding history of PID due to Chlamydia and gonorrhoea. No free fluid was seen in the pelvis and a CA-125 was normal. Abdominal computerised tomography confirmed the adnexal lesion but showed no additional masses. She had recently been investigated for menorrhagia and her endometrial biopsy and cervical cytology had been normal. She has type 2 diabetes and hypertension. On vaginal examination a large left sided pelvic mass was felt. At laparotomy there were dense adhesions between the adnexae, uterus, and bowel. The adnexae were completely obscured by scar tissues. She underwent hysterectomy left salpingo-oophorectomy and omental biopsy. Macroscopically, the left adnexa ( ?mm) hands a globular tan brown cystic appearance with a thickened fleshy wall and multiple fleshy projections into the lumen (Figure 1). A
Intramural leiomyomas of the bladder in asymptomatic men
Lopes, Roberto I.;Lopes, Roberto N.;Srougi, Miguel;
International braz j urol , 2003, DOI: 10.1590/S1677-55382003000300011
Abstract: bladder leiomyomas are rare benign mesenchymal tumors, which account for less than 0.43% of all bladder tumors with approximately 200 cases described in the literature. these tumors may be classified into 3 different locations: endovesical, intramural and extravesical. endovesical is the most common form, accounting for 63-86% of the cases, while intramural occurs in 3-7% and extravesical in 11-30%. the intramural form, especially small tumors, may not produce symptoms hardening detection. we report two cases of intramural bladder leiomyomas in asymptomatic men observed incidentally by transabdominal ultrasonography during the follow-up of benign prostatic hyperplasia. we discuss the diagnosis and management of these lesions.
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