The diffi culty in long-term expansion of mesenchymal stem cells (MSCs) using standard culture systems without the loss of their stem cell properties suggests that a critical feature of their microenvironment necessary for retention of stem cell properties is absent in these culture systems. We report here the reconstitution of a native extracellular matrix (ECM) made by human marrow cells ex vivo, which consists of at least collagen types I and III, fi bronectin, small leucine-rich proteoglycans such as biglycan and decorin, and major components of basement membrane such as the large molecular weight proteoglycan perlecan and laminin. Expansion of human MSCs on this ECM strongly promoted their proliferation, retained their stem cell properties with a low level of reactive oxygen species (ROS), and substantially increased their response to BMP-2. The quality of the expanded cells following each passage was further tested by an in vivo transplantation assay. The results showed that MSCs expanded on the ECM for multiple passages still retained the same capacity for skeletogenesis. In contrast, the bone formation capacity of cells expanded on plastic was dramatically diminished after 6-7 passages. These fi ndings suggest that the marrow stromal cell-derived ECM is a promising matrix for expanding largescale highly functional MSCs for eventual use in stem cell-based therapy. Moreover, this system should also be invaluable for establishment of a unique tissue-specifi c ECM, which will facilitate control of the fate of MSCs for therapeutic applications.

Salivary gland malignancies are rare tumors that comprise multiple histologic entities with diverse clinical behavior. Mucoepidermoid carcinoma is the most frequent primary salivary malignancy, followed by adenoid cystic and acinic cell carcinoma. Although most salivary malignancies are asymptomatic, presentation with a rapidly enlarging mass may be accompanied by pain, functional neurologic deficits, soft-tissue invasion, or nodal enlargement. Assessment of clinical behavior and physical exam greatly contributes to diagnostic workup. Preoperative imaging, to include ultrasound, computed tomography, or magnetic resonance imaging, may assist with surgical planning. Limitations of preoperative fine-needle aspiration cytology mean that, in some cases, definitive histologic diagnosis may not be established until therapeutic surgery is undertaken. Treatment strategies rely on oncologic resection of the primary site with negative margins as well as adjuvant radiotherapy in patients with high-risk features, such as high-grade histology, advanced T class, or perineural invasion. Regional lymphadenectomy is recommended for involved nodal basins. Patients with clinically node-negative disease at high risk for occult nodal metastases may be considered for elective lymphadenectomy or radiotherapy. Use of chemotherapy in the adjuvant setting, in combination with radiotherapy, remains controversial. The rate of objective response to palliative chemotherapy in recurrent or metastatic salivary gland malignancy remains low. In studies that include a significant proportion of adenoid cystic carcinomas, whether disease stability represents an indolent disease process or the true effect of a therapeutic drug may be difficult to discern. Recognition of genetic alterations and protein expression unique to salivary malignancies presents exciting new opportunities for molecularly targeted therapy, although the response to molecularly targeted therapy in studies has been modest thus far.

Doxazosin, if administered early, may be useful for preventing the prostate tumor formation, and also for limiting or completely suppressing the metastasis of prostate cancer in the TRAMP model. The mechanism of doxazosin is consistent with the established hypothesis.