Transcriptional profiling of uterine leiomyoma rats treated by a traditional herb pair, Curcumae rhizoma and Sparganii rhizoma

The aim of this study was to elucidate the concise effects of a traditional herb pair, Curcumae rhizoma-Sparganii rhizoma (CRSR), on uterine leiomyoma (UL) by analyzing transcriptional profiling. The UL rat model was made by intramuscular injection of progesterone and gavage administration of diethylstilbestrol. From 11 weeks of the establishment of the model, rats of the UL+CRSR group were gavaged daily with CRSR (6.67 g/kg). The serum concentrations of progesterone (P) and estradiol (E2) were determined by radioimmunoassay, the uterine index was measured by caliper measurement, and the pathological status was observed by hematoxylin and eosin stain. Gene expression profiling was checked by NimbleGen Rat Gene Expression Microarrays. The results indicated that the uterine mass of UL+CRSR rats was significantly shrunk and serum P and E2 levels significantly reduced compared to UL animals and nearly to the level of normal rats. Results of microarrays displayed the extensive inhibition of CRSR upon the expression of proliferation and deposition of extracellular matrix (ECM)-related genes, and significantly regulated a wide range of metabolism disorders. Furthermore, CRSR extensively regulated key pathways of the UL process, such as MAPK, PPAR, Notch, and TGF-β/Smad. Regulation of the crucial pathways for the UL process and ECM metabolism may be the underlying mechanisms of CRSR treatment. Further studies will provide clear clues for effectively treating UL with CRSR.

Leiomioma cutáneo atípico en un paciente con leiomiomatosis cutánea y mutación de la enzima fumarato hidratasa / Atypical leiomyoma in a patient with cutaneous leiomyomatosis and mutation of the enzyme fumarate hydratase

Se presenta un varón de 56 años con un leiomioma atípico en el contexto de una leiomiomatosis cutánea, con antecedentes familiares de miomatosis uterina y con estudio genético que revela una mutación en el gen de la enzima fumarato hidratasa, sin que hasta el momento presente ningún tipo de neoplasia maligna renal. El leiomioma atípico es un tumor poco frecuente, que usualmente ocurre de forma aislada, siendo excepcional la presentación en pacientes con leiomiomatosis cutánea. Es ampliamente conocida la relación de la mutación de la enzima fumarato hidratasa con leiomiomas mútiples, miomas uterinos y el mayor riesgo de desarrollar cáncer renal; sin embargo, el papel de esta mutación en el desarrollo de leiomiomas atípicos es por hoy imposible de esclarecer debido a los escasos casos recogidos en la literatura.

We report the case of a 56 year-old male with an atypical leiomyoma in the context of a cutaneous leiomyomatosis and a family history of uterine leiomyomatosis. The genetic study revealed a mutation in the gene for the enzyme fumarate hydratase, but he has not had any renal malignancy so far. Atypical leiomyoma is a rare tumor that usually presents as a single lesion and is exceptional in patients with cutaneous leiomyomatosis. The relation between fumarate hydratase enzyme mutations with multiple leiomyomas, uterine leiomyomatosis and an increased risk of developing kidney cancer is widely known. However, the role of these mutations in the development of atypical leiomyomas is still impossible to clarify given the few cases reported in the literature.

Effect of intramural myomectomy on endometrial HOXA10 and HOXA11 mRNA expression at the time of implantation window

HOXA11 and HOXA10 are expressed in endometrium throughout the menstrual cycle and show a dramatic increase during the mid-luteal phase at the time of implantation. The expression of these genes is decreased in women with myomas. To determine whether myomectomy would reverse HOXA11 and HOXA10 expression, we evaluated the transcript levels of these genes in the endometria of patients before and after myomectomy. Expression of HOXA11 and HOXA10 were examined prospectively during the midluteal phase in endometrium obtained from infertile women [n=12] with myoma before and three months after myomectomy. Endometrial HOXA11 and HOXA10 expression were evaluated using quantitative real-time reverse transcriptase-polymerase chain reaction [RT-PCR]. Endometrial HOXA11 and HOXA10 mRNAs expression levels [normalized to 18SrRNA] were increased insignificantly in endometrium of patients after myomectomy [p=0.7 and p=0.15 respectively]. The results suggest that the alteration in expression pattern of these genes could not account for some aspects of fertility after myomectomy

Polymorphic [CAG]n repeats in the androgen' receptor gene: a risk marker for endometriosis and uterine leiomyomas

Endometriosis and uterine leiomyomas are leading hormone responsive, benign uterine disordders responsible for high morbidity in women of reproductive age group. A polymorphic [CAG]n repeat length located in exon 1 of the androgen receptor [AR] gene has been proposed as a risk marker for both endometriosis and leiomyomas in some ethnic groups. The present study was carried out to assess the frequency of AR [CAG]n repeat polymorphism as a risk marker for endometriosis and uterine leiomyomas in Asian Indian women. DNA was isolated from peripheral blood samples of 331 subjects, which include 90 endometriosis cases, 140 cases of leiomyomas and 101 healthy age- and sex-matched controls. PCR was carried out to amplify exon 1 of the AR gene. All the PCR amplicons were analysed initially on 2% agarose gel electrophoresis, folllowed by bidirectional sequencing to calculate the number CAG repeats in individuals. The CAG repeat ranges detected in endometriosis cases were 4-33 [Mode-19] and in leiomyomas cases 5-34 [Mode-20], whereas in controls it was 5-34 [Mode-22]. A distinct variation was observed in the three groups at 14, 18, 19, 20 and 22 [CAG]n repeats, which were statistically analyzed using chi-square and odds ratio tests. 19 CAG repeats were found to be higher in endometriosis cases [19.09%] when compared with conttrols [9.04%], while 20 CAG repeats were higher in leiomyomas cases [14.02%] compared to controls [6.14%]. A statistically significant [P < 0.05] association was observed in 19 and 20 CAG repeats in endometriosis and leiomyomas, respectively. This is the first report from an Asian Indian population proposing that 19 and 20 CAG repeats of the AR gene are associated with endometriosis and leiomyoma and can be regarded as high-risk markers

Genética do leiomioma de útero / Genetics of uterine leiomyomata

Os leiomiomas de útero, também conhecidos como fibromas, säo tumores benignos de músculo liso geralmente associados com sangramento uterino intensivo, infertilidade e dor abdominal. Esses tumores säo considerados os mais frequentes em mulheres em idade reprodutiva constituindo um grave problema de saúde pública. Alteraçöes citogenéticas foram detectadas em cerca de 40 por cento dos leiomiomas, sendo que as anomalias cromossômicas mais frequentes incluem as translocaçöes entre os cromossomos 12q14-15 e 14q23-24, rearranjos no cromossomo 6 especificamente na banda p21 e deleçöes ou translocaçöes, envolvendo o cromossomo 7 na banda q22. Identificaçäo de rearranjos cromossômicos específicos, em leiomiomas uterinos, tem possibilitado a localizaçäo de regiöes do DNA prováveis de conter genes de relevante importância nesse processo. Através de técnicas de citogenética molecular foram identificados dois genes da família de proteínas näo histônicas do DNA, conhecidos como HMGIY e HMGIC. Esses dois genes apresentaram interrupçöes na sua sequência bem como alteraçöes na sua expressäo em fibróides com rearranjos 6p e t(12;14), respectivamente. Outros genes candidatos, possivelmente presentes nas demais aberraçöes cromossômicas observadas nos leiomiomas uterinos vêm sendo também investigados. Os estudos citogenéticos e moleculares, bem como a avaliaçäo de fatores étnicos e de predisposiçäo genética familial poderäo contribuir de forma significativa para elucidaçäo dos mecanismos de formaçäo desses tumores, bem como auxiliar no diagnóstico, prognóstico e prevençäo de leiomioma uterino.

Cytogenetic study of benign mesenchymal neoplasias

Três leiomiomas uterinos humanos foram cultivados e analisados citogeneticamente. Embora o número modal estivesse na regiäo diplóide, todas as neoplasias apresentaram hiperdiploidia. Um dos casos apresentou 27% das células na regiäo hipertriplóide-hipertraplóide. As alteraçöes numéricas mais frequentes foram monossomias envolvendo os cromossomos 20 (3 casos) e 2, 7, 18 (2 casos cada) e um caso apresentou polissomias de todos os cromossomos (variando de trissomia a pentassomia). Um caso apresentou um grande anel cromossômico semelhante ao cromossomo 1 e um marcador com o rearranjo: t(2;12) (2qter - 2q14-15 - 12 pter). O significado das alteraçöes citogenéticas em tumores benignos ainda está por ser determinada