No abstract

During embryo implantation, apoptosis is observed morphologically at the implantation site of endometrium. The objectives of this study were to demonstrate biochemical evidence of apoptosis and quantitative assessment of DNA fragmentation in uterine epithelial cells using a mouse implantation model, and to investigate the autocrine/paracrine regulation of apoptosis in uterine epithelial cells during blastocyst outgrowth. Blastocysts from day 4 pregnant mice were cultured on uterine epithelial cells for 96 h. Uterine epithelial cells dislodged by trophoblasts in endometrium-trophoblast unit demonstrated morphological features of apoptosis by Acridine Orange staining. Electrophoresis demonstrated DNA ladder and DNA fragmentation by enzyme-linked immunosorbent assay markedly increased after 48 h period of incubation. Apoptosis increased in an exponential way in accordance with trophoblast outgrowth. In addition, DNA fragmentation was shown in the epithelial cells by adding embryo-conditioned medium (CM) and the effect of embryo CM on apoptosis was significantly inhibited by anti-transforming growth factor (TGF)-beta antibody. Delayed outgrowth was observed after 48 h of incubation in the blastocysts cultured with anti-TGF-beta antibody. These results suggest there is autocrine/paracrine regulation of apoptosis in uterine epithelial cells at mouse embryo implantation and that TGF-beta might play an important role in the occurrence of apoptosis in the endometrium-trophoblast unit.

Isoflavones are known to exert anticancer effects. These effects were examined using two isoflavones, biochanin A and daidzein, in a mouse mammary tumor virus (MMTV)-induced spontaneous breast cancer model. Emphasis was placed on isoflavone metabolism by the intestinal microflora and changes in estrogen levels. Germ-free (Gf) mice and their conventionalized (Cv) counterparts were assigned to three diet groups: (1) control diet, (2) biochanin A and (3) daidzein. In all groups, urine was collected from virgin female mice to analyze isoflavone metabolism by high performance liquid chromatography. These studies revealed changes of biochanin A into genistein, and of daidzein into equol, which were accelerated in the Cv animals. However, the Gf mice could not transform biochanin A into genistein, or daidzein into equol. Estrogen levels in the control and daidzein diet groups were lower in the Gf mice than in the Cv mice. The biochanin A group showed no differences in estrogen levels between the Cv and Gf animals. Four-week-old male and female animals were paired in the Gf and Cv groups. The female animals delivered and lactated repeatedly and were observed for the development of mammary cancer by palpation, twice weekly, until 15 months of age. The Cv mice showed a significantly lower incidence of breast cancer in the biochanin A diet group than in the control or daidzein groups (p < 0.05). These results suggest that the anticarcinogenic effects in this system might be produced not by daidzein or equol, but by biochanin A and/or genistein. In the Gf animals, the incidence of breast cancer was significantly higher in the biochanin A group than in the control group (p < 0.05), probably due to the increased level of estradiol in the former group. The biochanin A group tended to have a higher incidence of breast cancer than the daidzein group in the Gf group, although no significant differences were noted. Thus, no anticarcinogenic effect was produced by biochanin A alone in the Gf mice. In view of the results presented, genistein derived from biochanin A following metabolic processes in the intestinal microflora most likely acts as an inhibitor in breast carcinogenesis; biochanin A is most likely a precursor of genistein.

In a clinical study using CEUS with 25% albumin, contrast-enhanced nodes were identified in all subjects. The pathologic findings suggested that any metastatic nodes observed were SLNs, indicating that this technique may represent a new modality for SLN identification.

Background Primary sarcoma of the breast is rare. Surgery has been the only curative treatment available. Recently, neoadjuvant chemotherapy including anthracycline/ifosfamide has been reported effective for patients with high-risk sarcomas in a prospective trial. Case presentation A 52-year-old Japanese woman presented with a mass in her left breast. The 10 cm tumor was fixed to her chest wall on examination. A skin biopsy was performed which showed leiomyosarcoma. Neoadjuvant chemotherapy was given and the tumor became mobile. A mastectomy and axillary dissection were performed with surgically negative margins. After neoadjuvant chemotherapy, the amount of necrosis was profoundly influenced by chemotherapy, and the histological effect of neoadjuvant chemotherapy was assessed in reference to pre-neoadjuvant chemotherapy magnetic resonance imaging. Conclusion In contrast to many other cancers, the evaluation of various treatments and of the histological effect of neoadjuvant chemotherapy for sarcoma has been difficult due to the rarity of these tumors. We report the case of a patient with a breast sarcoma, treated with neoadjuvant chemotherapy and discuss the appropriate pathological evaluation and therapeutic management.