Intracellular patterns of sialophorin expression define a new molecular classification of breast cancer and represent new targets for therapy.

BACKGROUND: Sialophorin is a transmembrane sialoglycoprotein. Normally, the molecule is only produced by white blood cells where it regulates functions such as intercellular adhesion, intracellular signalling, apoptosis, migration and proliferation. METHODS: Normal breast tissue and primary breast tumours were analysed by immunohistochemistry for sialophorin expression. The sialophorin-positive breast cancer cell line MCF7 was engineered to stably express either non-targeted or sialophorin-targeted small interfering RNA (siRNA). Assays were then performed in vitro to assess apoptosis, intracellular adhesion, transendothelial migration and cytotoxicity. An orthotopic mouse model assayed ability to produce tumours in vivo. RESULTS: Normal breast epithelial cells exhibit expression of the N-terminal domain of sialophorin in the cytoplasm but not the nucleus. The majority of these normal cells are also negative for expression of the C-terminal domain. In contrast, malignant breast epithelial cells exhibit N-terminal expression both in the cytoplasm and nucleus and the majority express the C-terminus in the nucleus. Using differential patterns of intracellular expression of the N and C termini of sialophorin, we define six subtypes of breast cancer that are independent of histological and receptor status classification. Targeting sialophorin with siRNA resulted in the MCF7 breast cancer cell line exhibiting increased homotypic adhesion, decreased transendothelial migration, increased susceptibility to apoptosis, increased vulnerability to lysis by natural killer cells and decreased ability to produce tumours in mice. CONCLUSION: Our results indicate that intracellular patterns of sialophorin expression define a new molecular classification of breast cancer and that sialophorin represents a novel therapeutic target.

Clinical features of clostridial bacteremia: a review from a rural area.

Blood samples, which were obtained from patients who lived in a rural area with approximately 500 acute-care hospital beds, were cultured from 1990 through 1997. We retrospectively reviewed the blood cultures that yielded Clostridium species (74 [0.12%] of 63,296 cultures). These were obtained from 46 different hospitalized patients (incidents per hospital, 0.03%). The source of the Clostridium species was a gastrointestinal site in 24 patients (52.2%). The most frequently identified Clostridium species was Clostridium perfringens (in 10 [21.7%] of patients), followed by Clostridium septicum (in 9 [19.6%]). Thirty-one patients (67.4%) were aged > or =65 years, 13 patients (28.3%) had diabetes mellitus, and underlying malignancy was present in 22 patients (47.8%). The mortality rate of patients whose condition had been managed surgically was 33%; for those patients whose conditions required medical management, the mortality rate was 58%. Clostridium bacteremia in these patients usually had a gastrointestinal source, it often occurred in patients with serious underlying medical conditions, and it rarely was the result of traumatic farm accidents.

Pseudomonas aeruginosa infections of intact skin.

Pseudomonas aeruginosa infections of healthy skin are uncommon. We report four cases of P. aeruginosa infections of intact skin. These cases illustrate the clinical spectrum of these cutaneous infections: localized, mild epidermal infections (the green nail syndrome and webbed space infections), moderately serious infections (cutaneous folliculitis and otitis externa), and, in immunocompromised patients, extremely serious infections (malignant otitis externa, perirectal infection, and ecthyma gangrenosum).

Granulomas of the vocal cords caused by Sporothrix schenckii.

A 42-year-old female acquired an acute respiratory infection one week after working in a sphagnum moss packing plant. Three and one half months later direct laryngoscopic examination, done because of persistent hoarseness, revealed granulomas of the left true cord. Initial biopsy showed noncaseating granulomas, and a repeat biopsy with fungal cultures grew Sporothrix schenckii. The patient was treated with an oral solution of saturated potassium iodide and gradually improved although mild hoarseness has persisted.

Nitrofurantoin-induced granulomatous hepatitis.

Nitrofurantoin has been described as a cause of both hepatocellular cholestatic hepatic injury. A case report of a patient in whom granulomatous hepatitis developed attributed to nitrofurantoin is given.