Disease relevance of Leiomyoma

• In human subjects with uterine fibroids, asoprisnil suppressed both the duration and intensity of uterine bleeding in a dose-dependent manner and reduced tumor volume in the absence of estrogen deprivation [1].
• Second, molecular alterations in stromal cells favor binding of transcriptional enhancers versus inhibitors to a normally quiescent aromatase promoter and initiate transcription (breast/endometrial cancer, endometriosis, and uterine fibroids) [2].
• In the present report we describe the detection of human IGF-I RNAs (both type Ia and type Ib) and IGF-II RNAs in benign (leiomyoma) and malignant (leiomyosarcoma) tumours from smooth muscle origin, using Northern blot hybridization analysis [3].
• Germline mutations in FH predispose individuals to leiomyomas and renal cell cancer (HLRCC), whereas mutations in SDH cause paragangliomas and phaeochromocytomas (HPGL) [4].
• Biallelic inactivation of FH was found in one uterine leiomyosarcoma, one cutaneous leiomyoma, and one soft tissue sarcoma [5].

Psychiatry related information on Leiomyoma

• Based on the evidence available, the panel proposed a number of subgroups of postmenopausal women with vasomotor symptoms in whom tibolone might have added value; these included women with sexual dysfunction, mood disorders, fibroids and urogenital complaints, as well as those with breast tenderness or high mammographic breast density with EPT use [6].
• Vasectomized copulations protect against fibroids, an observation that undermines the steroid hypothesis and supports our hypothesis [7].

High impact information on Leiomyoma

• Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer [8].
• Estradiol-dependent uterine leiomyomas in transgenic mice [9].
• Uterine leiomyomas are a major health problem for women of reproductive age [9].
• The mitogenic activity of the leiomyoma extract throughout purification was tested by tritiated thymidine incorporation and DNA content in NIH/3T3 fibroblasts and KW human smooth muscle-like cells [10].
• These data suggest that LDGF may participate in the pathophysiology of uterine leiomyomas [10].

Chemical compound and disease context of Leiomyoma

• Goserelin therapy before surgery for uterine fibroids [11].
• Presence of an insulin-like growth factor I autocrine loop predicts uterine fibroid responsiveness to tamoxifen [12].
• More PGs containing mainly chondroitin sulfate could be detected in malignant tumors (leiomyosarcomas) than in benign tumors (leiomyomas and fibromas) [13].
• Uterine myometria and spontaneous leiomyomas from the Eker rat, which carries a germ-line mutation in the tuberous sclerosis complex-2 (Tsc2) tumor suppressor gene, were analyzed for genetic defects in and expression of the Tsc2 and HMGA proteins [14].
• These results warrant further investigation into the possibility that heparin might be useful in the treatment of uterine fibroids [15].

Biological context of Leiomyoma

• We show that FH mutations alter significantly the expression profiles of fibroids, most strikingly increasing the expression of genes involved in glycolysis [16].
• Genes with lower expression in FH-mutant fibroids belonged to groups such as extracellular matrix, cell adhesion, muscle development and cell contraction [16].
• Exogenous IGF-I stimulated ELT 3 cell proliferation, confirming that this growth factor is mitogenic for leiomyoma cells [12].
• Uterine leiomyoma is an estrogen-responsive tumor, and the present studies examine the ability of the antiestrogen tamoxifen to modulate leiomyoma cell growth [12].
• Loss of heterozygosity and reduced expression of the CUTL1 gene in uterine leiomyomas [17].

Anatomical context of Leiomyoma

• The expression of PAI-1 mRNA was higher in 11 (68.75%) of 16 leiomyomas compared with the adjacent myometrium (leiomyoma/myometrium ratio, 1.4-3.0; mean, 2.045) [18].
• No structural alterations were observed at the HMGA2 locus in either primary rat leiomyomas or leiomyoma-derived cell lines that expressed HMGA2 [14].
• Somatic deletion of the 5' ends of both the COL4A5 and COL4A6 genes in a sporadic leiomyoma of the esophagus [19].
• As in subgroups of pleomorphic adenomas of the salivary glands, leiomyomas of the uterus, and lipomas with 12q14-15 abnormalities the HMGI-C gene is frequently rearranged we tested PCH with either 12q14-15 abnormalities or normal karyotype by FISH and 3' RACE experiments for rearrangements of HMGI-C [20].
• The present results suggest that the abundant expression of Bcl-2 protein may have a molecular basis characteristic of leiomyomas in the human uterus and that progesterone may play a vital role in the enhanced expression of Bcl-2 protein in human uterine leiomyoma cells [21].

Gene context of Leiomyoma

• Concomitantly, HMGA2 protein, which was completely absent in normal myometria, was expressed in 16 of 19 Eker leiomyomas [14].
• HMGA1 was expressed in both leiomyoma and normal myometria [14].
• Eker leiomyomas exhibited a 50% incidence of loss of the wild-type Tsc2 allele and an almost uniform loss of protein expression, implicating loss of function of the Tsc2 gene in these tumors [14].
• We demonstrate here the occurrence of a somatic deletion at the COL4A5/COL4A6 locus at Xq22 in a frozen leiomyoma sample [19].
• In addition, not only leiomyosarcoma, but also leiomyoma specimens that exhibited negligible levels of complex expression, manifested detectable cdk2 activity [22].

Analytical, diagnostic and therapeutic context of Leiomyoma

• We purified the major mitogen for human smooth muscle-like cells in leiomyoma extracts by sequential liquid chromatography on (a) carboxymethyl-Sepharose, (b) heparin-Sepharose columns, (c) cartridges of C18 silica, and (d) linear gradient reverse-phase high performance liquid chromatography [10].
• We have examined the presence of mRNA encoding both IGF-I and IGF-II and IGFBP-1, -2, and -3 in fibroids and corresponding myometrium from 20 women undergoing hysterectomy for symptomatic uterine fibroids [23].
• The messenger RNA (mRNA) content was analyzed by RT-PCR. mRNAs for c-fos, c-myc, c-jun, ER, and PR were detected in all 18 samples of leiomyoma and corresponding myometrial tissue collected in this study [24].
• The effects of sex steroids on p53 protein content in cultured leiomyoma cells were also assessed by Western immunoblot analysis [25].
• This study examines p53 expression and mutation of the p53 gene in benign and malignant smooth muscle tumours of the uterine corpus. p53 expression was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded tissue from 23 leiomyosarcomas, 10 tumours of uncertain malignant potential (TUMPs), and 18 leiomyomas [26].

References