May Sonic Hedgehog proteins be markers for malignancy in uterine smooth muscle tumors?

Several studies have demonstrated that the Sonic Hedgehog signaling pathway (SHH) plays an important role in tumorigenesis and cellular differentiation. We analyzed the protein expression of SHH pathway components and evaluated whether their profile could be useful for the diagnosis, prognosis, or prediction of the risk of malignancy for uterine smooth muscle tumors (USMTs). A total of 176 samples (20 myometrium, 119 variants of leiomyoma, and 37 leiomyosarcoma) were evaluated for the protein expression of the SHH signaling components, HHIP1 (SHH inhibitor), and BMP4 (SHH target) by immunohistochemistry. Western blot analysis was performed to verify the specificity of the antibodies. We grouped leiomyoma samples into conventional leiomyomas and unusual leiomyomas that comprise atypical, cellular, mitotically active leiomyomas and uterine smooth muscle tumors of uncertain malignant potential. Immunohistochemical analysis showed that SMO, SUFU, GLI1, GLI3, and BMP4 expression gradually increased depending on to the histologic tissue type. The protein expression of SMO, SUFU, and GLI1 was increased in unusual leiomyoma and leiomyosarcoma samples compared to normal myometrium. The inhibitor HHIP1 showed higher expression in myometrium, whereas only negative or basal expression of SMO, SUFU, GLI1, and GLI3 was detected in these samples. Strong expression of SHH was associated with poorer overall survival. Our data suggest that the expression of SHH proteins can be useful for evaluating the potential risk of malignancy for USMTs. Moreover, GLI1 and SMO may serve as future therapeutic targets for women with USMTs.

Psychosexual perspectives of the husbands of women treated with an elective hysterectomy.

The purpose of this study was to explore the psychosexual perspectives of a group of Brazilian men whose wives underwent an elective hysterectomy. A qualitative design based on the narrative analysis method was used to interview 22 husbands. Results showed similarities and differences among husbands regarding the support provided to their wives, the notion of sexual absence in the postsurgical period, the notion of sexual pleasure after the hysterectomy, and feelings regarding the impossibility of having children. The authors conclude that personal care requirements should be identified and satisfied to provide comprehensive and meaningful care.

Genic expression of the uterine leiomyoma in reproductive-aged women after treatment with goserelin.

OBJECTIVE: To identify the genes presenting different expression in uterine leiomyomas after goserelin treatment. DESIGN: Retrospective analyses of tissue obtained in a prospective clinical study. SETTING: School of Medicine of the University of São Paulo. PATIENT(S): 30 nulliparous black women aged 20 to 45 years with symptoms of uterine leiomyoma, uterine volume over 300 mL, and surgical indications for myomectomy. INTERVENTION(S): Fifteen patients were given a monthly dose of 3.6 mg of goserelin over 3 months before surgery (group A), and 15 patients underwent surgery without any previous treatment (group B). Five random samples from each group were analyzed using the microarray technique with the Affymetrix platform (GeneChip Rat Genome 230 2.0 Array). MAIN OUTCOME MEASURE(S): Quantification of transcript expression levels of uterine fibroids in patients treated or not treated with goserelin. RESULT(S): Of the total of 47,000 sequences that were analyzed, representing approximately 38,500 human genes already characterized, we found a differential expression of 174 genes. Of these, 70 were up-regulated (33 genes with known function) and 104 were down-regulated (65 genes with known function) in samples from group A (treated) when compared with group B (nontreated). CONCLUSION(S): The genic expression of uterine leiomyomas changes in women who have had goserelin treatment when compared with nontreated patients.

Action of aromatase inhibitor for treatment of uterine leiomyoma in perimenopausal patients.

OBJECTIVE: To assess the effect of the aromatase inhibitor on patients with leiomyoma in the reproductive stage regarding reduction of uterine volume and control of symptoms. DESIGN: Clinical study. SETTING: Academic clinical practice. PATIENT(S): Twenty patients, over 35 years of age, with symptomatic uterine leiomyoma. INTERVENTION(S): Anastrozol, 1 mg/day for 12 weeks. MAIN OUTCOME MEASURE(S): Measurement of uterine volume, assessment of symptoms related to uterine leiomyoma, serum assay of follicle stimulating hormone (FSH), and estradiol. RESULTS: Average reduction of uterine volume of 9.32%, attaining up to 32%, and reduction of symptoms of uterine leiomyoma (menstrual volume, duration of menstruation, and dysmenorrhea). No significant change in serum levels of FSH and estradiol during use of the medication were observed. CONCLUSION(S): Anastrozol proved to be effective in reducing the volume of the uterus-leiomyoma structure, leading to the control of symptoms connected with the disorder without changes in serum FSH and estradiol.

Embolização do mioma uterino sintomático / Symptomatic uterine fibroid embolization

Descrição dos principais aspectos da embolização do mioma uterino (EMU) sintomático, utilizando dados iniciais da casuística pessoal e revisão de literatura via Medline. A literatura demonstra melhora importante do sangramento uterino e dor pélvica após a EMU. A redução volumétrica dos nódulos de mioma e do útero após a EMU é observada em diversos estudos. O tempo de permanência hospitalar e recuperação pós EMU é menor quando comparado com a histerectomia ou miomectmia. Trabalhos randomizados ainda não foram executados para determinar qual é o melhor agente embolizante, duração da resposta clínica ao tratamento, efeitos na fertilidade e freqüência de complicações. Relatos de caso de gestação pós-EMU são descritos. A EMU representa alternativa terapêutica para o tratamento do mioma uterino. Em nossa casuística, a EMU é efetiva no controle dos sintomas e redução do volume uterino com baixa incidência de complicações. Em casos selecionados pode ser indicada a mulheres com desejo reprodutivo.

O Inibidor da aromatase na terapia endócrina do câncer de mama / Aromatase inhibitor in breast cancer endocrine therapy

Câncer de mama é o tumor maligno mais freqüente nas mulheres. O tratamento para pacientes com este tipo de câncer envolve medidas locais e sistêmicas. Entre os tratamentos sistêmicos destaca-se a terapia endócrina, baseada na contraposição do estímulo estrogênio ao desenvolvimento tumoral. O Tamoxifeno tem papel central entre as drogas utilizadas com essa finalidade, e atualmente os inibidores da aromatase vêm despontando como tratamento bastante promissor em várias circunstâncias. Entre elas estão o tratamento de primeira linha para mulheres com câncer de mama metastático ou localmente avançado, com receptor estrogênico positivo ou desconhecido, câncer de mama em paciente pós-menopausa com progressão da doença após terapia antiestrogênica, tratamento adjuvante contra o câncer de mama em estágio inicial, adjuvância estendida e neoadjuvância

Comparative study of different dosages of goserelin in size reduction of myomatous uteri.

STUDY OBJECTIVE: To compare uterine size reduction obtained with three monthly subcutaneous injections of 3.6 mg of goserelin versus a single subcutaneous injection of 10.8 mg. DESIGN: Prospective, randomized clinical trial (Canadian Task Force classification I). SETTING: Department of Gynecology and Obstetrics at the Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo. PATIENTS: Forty-five premenopausal women with uterine leiomyomas and uterine size greater than 600 cm(3) randomized to one of two groups. INTERVENTION: Group A: 23 women received three monthly subcutaneous 3.6-mg doses of goserelin. Group B: 22 women received a single subcutaneous injection of 10.8 mg of goserelin. Follicle-stimulating hormone (FSH), estradiol, and hemoglobin levels were measured monthly. After 3 months, uterine size was determined by transvaginal and/or abdominal ultrasound. MEASUREMENTS AND MAIN RESULTS: In group A, mean reduction of uterine size was 43% (426 cm(3)) at the end of treatment. In Group B, mean reduction of uterine size was 54% (494 cm(3)). Serum levels of FSH and estradiol were in postmenopausal range during treatment. Hemoglobin level improvement was equivalent in both groups. CONCLUSION: Use of single injection of 10.8 mg of goserelin promoted significantly greater reduction in uterine size than three monthly 3.6-mg injections in patients with voluminous uterine leiomyomas.

Protocolo da extraçäo de DNA de material parafinado para análise de microssatélites em leiomioma / DNA extraction from paraffin material protocol in order to analyse microssatellites in uterine leiomyoma

É apresentada a padronizaçäo de protocolo de extraçäo de DNA de material parafinado para análise da instabilidade de microssatélites de genes relacionados ao leiomioma uterino, utilizando-se 30mg a 40mg de tecido retirado de blocos de parafina. Os blocos säo desparafinizados por banhos de xilol a 65ºC, reidratados com soluções de concentrações decrescentes de ETOH e água deionizada. A extraçäo de DNA é obtida através das etapas de lise celular, com soluçäo Promega, digestäo de proteínas por proteinase K, precipitaçäo com proteínas com soluçäo Promega e precipitaçäo do DNA com ETOH 70 por cento gelado e ressuspendido com soluçäo Promega. Este protocolo resulta em um DNA viável para uso na reaçäo em cadeia da polimerase (PCR)

Effects of treatment with gonadotropin releasing hormone agonist on the uterine leiomyomata structure.

OBJECTIVE: Our aim was to study the effects of the gonadotropin releasing hormone agonist on the uterine leiomyoma of infertile women. MATERIAL AND METHODS: Sixty-seven nulliparous women (aged 24-39 years) with uterine leiomyomas, underwent ultrasonographic study of leiomyoma volume, and were divided in two groups. Thirty-one had nodes greater than 300 cm3 and were treated with goserelin 3.6 mg every 28 days for 6 months (group I); the other 36 patients did not receive medication (group II or control group). Sixteen patients from group I had < or = 36% (median) reduction of the leiomyoma volume (subgroup Ia) and the other 15 women had reduction > 36% (subgroup Ib). All women underwent myomectomy. RESULTS: The group with the greater leiomyoma reduction after treatment with goserelin (group Ib) showed a significantly lower percentage of ER+ when compared with group Ia and the control group. Group Ib had a significantly higher percentage of PR+ in relation to the control group, but not to group Ia. The number of blood vessels, AgNOR dots, and cells, and the amount of collagen were not different between the three groups studied. Leiomyomata reduction correlated negatively with the percentage ER+ cells, but positively with the PR+ cells, amount of collagen and number of blood vessels. No correlation was found between the number of AgNOR dots and cellularity. CONCLUSION: Our data strengthen the hypothesis that the uterine leiomyoma response to steroid hormones results from the presence of specific hormone receptors, and progesterone receptors may also play a role in the development of leiomyoma.

Tratamento dos leiomiomas por embolizaçäo das artérias uterinas / Uterine artery embolization in the treatment of uterine leiomyomas

Objetivos: avaliar os resultados da embolizaçäo das artérias uterinas (EAU) como tratamento do leiomioma uterino. Métodos: foram estudadas 18 mulheres com diagnóstico ultra-sonográfico de leiomioma uterino submetidas à EAU com partículas de álcool polivinílico (PVA). O acesso arterial foi realizado por punçäo da artéria femoral e a progressäo do cateter foi monitorada até atingir seletivamente as artérias uterinas. A avaliaçäo dos resultados foi realizada pelo estudo ultra-sonográfico antes e três meses após o procedimento. Foi realizado controle clínico evolutivo para avaliaçäo das características menstruais e do volume uterino. Resultados: houve insucesso técnico em três casos por dificuldade de cateterizaçäo das artérias uterinas. O sangramento e a dismenorréia foram controlados no intervalo de três meses em 86 e 60 por cento das pacientes, respectivamente. A média dos volumes uterinos iniciais foi de 381 cmü e após 3 meses foi de 263 cmü. Houve reduçäo média de 27,4 por cento no volume uterino três meses após o tratamento. Três pacientes tiveram insuficiência ovariana clínica e laboratorial (20 por cento dos casos). Conclusöes: a EAU representa alternativa terapêutica para o tratamento dos leiomiomas uterinos. Em virtude do risco de insuficiência ovariana esse procedimento é reservado para pacientes com mais de 45 anos de idade ou com prole completa.

Estudos das caracteristicas anatomopatologicas do utero de mulheres por miomatose uterina / Study of anatomopathological features of uterus of women submitted to hysterectomy my for uterine myomatosis

O mioma do utero e patologia de elevada incidencia em ginecologia e a sintomatologia que o acompanha e caracteristica. Muitas vezes, entretanto, esta associado a outras causas de apresentacao clinica semelhante, e somente o estudo anatomopatologico...

Gestaçäo após tratamento clínico de mioma com goserelin: relato de caso e discussäo / Pregnancy after clinic treatament of uterine mioma with goserelin: description of one case

Paciente portadora de mioma uterino com 34 anos, nuligesta, desejosa de gravidez. Proposto tratamento com análogos do GnRH e posterior cirurgia (miomectomia). Após o tratamento clínico a paciente ficou gravida e neste trabalho discute-se a importância do tratamento cirurgico após o uso de medicamentos para reduçäo do volume uterino

Uso de analogo do GNRH no tratamento do sangramento uterino anormal: relato de um caso de aplasia medular / GNRH analogue in the treatment of abnormal uterine bleeding: a case report of aplastic anemia

Objetivo: apresentar um caso de aplasia medular severa com sangramento uterino recidivante controlado com goserelin, um analogo do GnRH. Relato do caso: Paciente de 18 anos, raça amarela, nuligesta, com manifestaçäo inicial de moniliase bucal, palidez cutânea progressiva, petequias e equimose pelo corpo, adenopatia generalizada e amenorreia. O hemograma revelou pancitopenia acentuada e o mielograma confirmou o diagnóstico de aplasia medular. Näo houve doador compatível para transplante de medula ossea. Após sucessivas transfusöes sanguineas e plaquetarias, evoluiu com metrorragias recidivantes apesar do emprego de altas doses de hormonios esteróides...

Tratamento do mioma uterino / Uterine leiomyoma treatment

Os autores relatam os recursos clinicos e cirurgicos para terapeutica do mioma uterino dando enfase nos mais recentes como a utilizacao dos analogos do GmRH. Destacam a importancia de avaliar cada caso antes de instituir a terapeutica, quanto a sintomatologia, desejo de gravidez, idade da paciente, tamanho do tumor. Descrevem tambem as vantagens e desvantagens e efeitos colaterais de cada condicao terapeutica.