17-Beta-estradiol induces transformation and tumorigenesis in human breast epithelial cells.

Breast cancer is a malignancy whose dependence on estrogen exposure has long been recognized even though the mechanisms whereby estrogens cause cancer are not clearly understood. This work was performed to determine whether 17beta-estradiol (E2), the predominant circulating ovarian steroid, is carcinogenic in human breast epithelial cells and whether nonreceptor mechanisms are involved in the initiation of breast cancer. For this purpose, the effect of four 24 h alternate periods of 70 nM E2 treatment of the estrogen receptor alpha (ER-alpha) negative MCF-10F cell line on the in vitro expression of neoplastic transformation was evaluated. E2 treatment induced the expression of anchorage-independent growth, loss of ductulogenesis in collagen, invasiveness in Matrigel, and loss of 9p11-13. Only invasive cells that exhibited a 4p15.3-16 deletion were tumorigenic. Tumors were poorly differentiated ER-alpha and progesterone receptor-negative adenocarcinomas that expressed keratins, EMA, and E-cadherin. Tumors and tumor-derived cell lines exhibited loss of chromosome 4, deletions in chromosomes 3p12.3-13, 8p11.1-21, 9p21-qter, and 18q, and gains in 1p, and 5q15-qter. The induction of complete transformation of MCF-10F cells in vitro confirms the carcinogenicity of E2, supporting the concept that this hormone could act as an initiator of breast cancer in women. This model provides a unique system for understanding the genomic changes that intervene for leading normal cells to tumorigenesis and for testing the functional role of specific genomic events taking place during neoplastic transformation.

A Review of Sleeve Gastrectomy Specimen Histopathology.

With the increasing popularity of sleeve gastrectomy, many stomach specimens are being evaluated. Understanding the significance and treatment for unexpected pathology is important. This study examines the incidence of relevant histopathology of sleeve gastrectomy specimens. It evaluates previous data for each histopathology and provides recommendations for treatment. In this study, a retrospective review was performed for 241 patients who underwent sleeve gastrectomy from 2009 to 2014 at a single institution. Of the specimens, 122 had no significant histopathology, 91 had gastritis, 13 had lymphoid aggregates, 5 had hyperplasia, 3 had intestinal metaplasia, 3 had gastrointestinal stromal tumors (GISTs), and 3 had gastric polyps. Of the GISTs all had a low mitotic rate and the size of the tumor ranged from 1.5 to 4.5 cm. The findings of metaplasia may be a marker for increased risk of malignancy and may require additional surveillance. The findings of GIST may warrant interval imaging to survey for recurrence, though the likelihood of recurrence for the tumors in this study is less than 2 per cent based on previous studies.

The estrogen antagonist ICI-182-780 does not inhibit the transformation phenotypes induced by 17-beta-estradiol and 4-OH estradiol in human breast epithelial cells.

Prolonged unopposed estrogen exposure is a widely accepted risk factor in breast cancer development. However, the mechanisms through which estrogens induce breast carcinogenesis have not been definitively unraveled. For testing whether estrogens exert their transforming effects through a non-receptor-mediated mechanism, we have treated the spontaneously immortalized human breast epithelial cells MCF-10F, which are estrogen receptor alpha negative, with 17-beta estradiol (E(2)) or its metabolite 4-OH-estradiol (4-OH-E(2)), each one either alone or in combination with the antiestrogen ICI-182-780. Treated cells were maintained for several passages in culture and evaluated for colony formation in agar-methocel (CE), tri-dimensional growth in collagen matrix, invasiveness in matrigel, and cell cycle analysis by flow cytometry. Both E(2) and 4-HO-E(2), at all the doses tested, in the presence or absence of ICI-182-780, increased CE and decreased the cells' ductulogenic capacity. They also increased the invasiveness and the number of cells in the S phase of the cell cycle. Our data clearly demonstrate that E(2) and 4-OH-E(2) increase cell proliferation and induce transformation in MCF-10F cells, phenomena that are not abrogated by ICI-182-780. The failure of the antiestrogen to abrogate the transformation phenotypes led us to hypothesize that estrogen-induced transformation is occurring by a non-estrogen receptor alpha-mediated process, more probably through the genotoxic effect of the estrogen metabolite 4-HO-E(2).

Delayed hemopericardium and associated pericardial mass after blunt chest trauma.

The finding of a pericardial effusion in the pediatric population evokes an extensive list of differential diagnoses. With the added history of trauma the effusion should be considered secondary to hemorrhage. We present a patient with such a history who was admitted to the hospital with the finding of a large pericardial effusion and an associated pericardial mass. The evaluation and treatment of this rare pathology are discussed as well as a review of the literature.

Mycoplasma pneumoniae associated with hemolytic anemia, cold agglutinins, and recurrent arterial thrombosis.

A 40-year-old white male developed Mycoplasma pneumoniae pneumonia (IgM titer 1:256) as well as autoimmune hemolytic anemia due to cold agglutinins (titer of 1:512). Four days after admission to the hospital, he developed an acute superior mesenteric artery (SMA) thrombosis. Four feet of ischemic small bowel were resected. A follow-up angiogram again showed SMA thrombosis and a left popliteal artery thrombosis. The patient was returned to the operating room and underwent thrombectomy of the affected arteries. The following day, he again developed a left popliteal artery thrombosis requiring thrombectomy. Plasmapheresis, Coumadin and prednisone were implemented. No further thrombotic events occurred. Hypercoagulability workup was negative. Pathology samples revealed vasculitis. Based on a negative hypercoagulability workup, nonrecurrence of thrombotic events after treatment, and in the absence of any structural abnormalities of the affected arteries, an autoimmune phenomenon with damage to the endothelium was thought to have played a role in the mechanism of thrombosis.