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.

A high concentration of genistein down-regulates activin A, Smad3 and other TGF-beta pathway genes in human uterine leiomyoma cells

Previously, we found that high doses of genistein show an inhibitory effect on uterine leiomyoma (UtLM) cell proliferation. In this study, using microarray analysis and Ingenuity Pathways Analysis(TM), we identified genes (up- or down-regulated, > or = 1.5 fold, P < or = 0.001), functions and signaling pathways that were altered following treatment with an inhibitory concentration of genistein (50 microg/ml) in UtLM cells. Downregulation of TGF-beta signaling pathway genes, activin A, activin B, Smad3, TGF-beta2 and genes related to cell cycle regulation, with the exception of the upregulation of the CDK inhibitor P15, were identified and validated by real-time RT-PCR studies. Western blot analysis further demonstrated decreased protein expression of activin A and Smad3 in genistein-treated UtLM cells. Moreover, we found that activin A stimulated the growth of UtLM cells, and the inhibitory effect of genistein was partially abrogated in the presence of activin A. Overexpression of activin A and Smad3 were found in tissue samples of leiomyoma compared to matched myometrium, supporting the contribution of activin A and Smad3 in promoting the growth of UtLM cells. Taken together, these results suggest that down-regulation of activin A and Smad3, both members of the TGF-beta pathway, may offer a mechanistic explanation for the inhibitory effect of a high-dose of genistein on UtLM cells, and might be potential therapeutic targets for treatment of clinical cases of uterine leiomyomas.

Myxoid leiomyoma of tunica vaginalis testis.

Myxoid leiomyoma is an extremely rare tumor, presenting as a scrotal mass. We report a case of 60 years male, who presented with a painless scrotal mass and operated as secondary hydrocoele. This lesion should be differentiated from other myxoid tumors and tumors with myxoid degeneration.

Galactosaminoglycans from normal myometrium and leiomyoma

In many tumors, the amount of chondroitin sulfate in the extracellular matrix has been shown to be elevated when compared to the corresponding normal tissue. Nevertheless, the degree of chondroitin sulfate increase varies widely. In order to investigate a possible correlation between the amount of chondroitin sulfate and tumor size, several individual specimens of human leiomyoma, a benign uterine tumor, were analyzed. The glycosaminoglycans from eight tumors were extracted and compared with those from the respective adjacent normal myometrium. The main glycosaminoglycan found in normal myometrium was dermatan sulfate, with small amounts of chondroitin sulfate and heparan sulfate. In leiomyoma, both dermatan sulfate and chondroitin sulfate were detected and the total amounts of the two galactosaminoglycans was increased in all tumors when compared to normal tissue. In contrast, the heparan sulfate concentration decreased in the tumor. To assess the disaccharide composition of galactosaminoglycans, these compounds were incubated with bacterial chondroitinases AC and ABC. The amounts of L-iduronic acid-containing disaccharides remained constant, whereas the concentration of D-glucuronic acid-containing disaccharides increased from 2 to 10 times in the tumor, indicating that D-glucuronic acid-containing disaccharides are responsible for the elevation in galactosaminoglycan concentration. This increase is positively correlated with tumor size

Immunohistochemical identification of mesenchymal tumors of the gastrointestinal tract

El origen de los tumores mesenquimáticos del tracto gastrointestinal tradicionalmente considerados musculares ha sido recientemente debatido postulándose que algunos de ellos serían en realidad derivados de células del sistema nervioso periférico. En el presente trabajo hemos estudiado una serie de tumores mesenquimáticos digestivos empleando un antisuero para S-100 y dos antisueros para proteínas de filamentos intermedios: la proteína gliofibrilar ácida (PGFA), y la desmina. La técnica utilizada fue la de peroxidasa-antiperoxidasa empleando antisueros policlonales obtenidos de DAKO (Dinamarca). Se estudiaron 24 tumores mesenquimáticos del tracto digestivo (Tabla 1). Las localizaciones fueron: 1 de esófago, 16 de estómago, 6 de intestino delgado y 1 de colon. Los mismos fueron diagnosticados como: leiomioma (18 casos), leiomioblastoma (3 casos) y leiomiosarcomas (3 casos). Como grupo control se estudiaron 5 leiomiomas uterinos. Estos resultaron uniformemente positivos para desmina y negativos para S-100 y PGFA. Diez casos fueron positivos con el antisuero para desmina; correspondiendo éstos a 9 leiomiomas y 1 leiomioblastoma (Tabla 2). Seis (25%) de los tumores expresaron marcadores neurales: 5 fueron positivos con S-100, 4 con PGFA y correspondieron a 3 leiomiomas, 1 leiomioblastoma y 2 leiomiosarcomas. En ningún tumor se observó tinción simultánea para desmina y algunos de los marcadores neurales. Ocho casos (33%) fueron negativos con todos los antisueros empleados siendo: 6 leiomiomas; 1 leiomioblastoma y 1 leiomiosarcomas. Nuestros resultados sugieren la existencia de por lo menos dos grupos de tumores de acuerdo a sus características inmunohistoquímicas: aquellos de origen miogénico y los derivados de células del sistema periférico. Los tumores negativos para ambos grupos de marcadores podrán probablemente ser clasificados mediante otras técnicas inmunohistoquímicas o ultraestructurales...