Chemotherapy-Induced Depletion of OCT4-Positive Cancer Stem Cells in a Mouse Model of Malignant Testicular Cancer.

Testicular germ cell tumors (TGCTs) are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse TGCT model featuring germ cell-specific Kras activation and Pten inactivation. The resulting mice developed malignant, metastatic TGCTs composed of teratoma and embryonal carcinoma, the latter of which exhibited stem cell characteristics, including expression of the pluripotency factor OCT4. Consistent with epidemiological data linking human testicular cancer risk to in utero exposures, embryonic germ cells were susceptible to malignant transformation, whereas adult germ cells underwent apoptosis in response to the same oncogenic events. Treatment of tumor-bearing mice with genotoxic chemotherapy not only prolonged survival and reduced tumor size but also selectively eliminated the OCT4-positive cancer stem cells. We conclude that the chemosensitivity of TGCTs derives from the sensitivity of their cancer stem cells to DNA-damaging chemotherapy.

Genetic testing utilization and the role of the laboratory genetic counselor.

Laboratory genetic counselors within hospital laboratories and genetic testing laboratories have an important role in increasing the appropriate utilization of genetic tests. This service is becoming more important as genetic testing becomes more complex and the demand for genetic testing in healthcare increases. Additionally genetic tests are among the most expensive assays in the clinical laboratory test catalog. Laboratory genetic counselors are able to increase genetic test utilization through review and assessment of the appropriateness of the ordered testing, developing protocols, and by increasing communication with ordering providers.

Designing a tubular matrix of oriented collagen fibrils for tissue engineering.

A scaffold composed entirely of an extracellular matrix component, such as collagen, with cellular level control would be highly desirable for applications in tissue engineering. In this article we introduce a novel, straightforward flow processing technique that fabricates a small diameter tubular matrix constructed of anisotropic collagen fibrils. Scanning electron microscopy confirmed the uniform alignment of the collagen fibrils and subsequent matrix-induced alignment of human fibroblasts. The uniform alignment of the fibroblasts along the collagen fibrils demonstrated the ability of the aligned fibrils to successfully dictate the directional growth of human fibroblasts through contact guidance. Various non-cytotoxic cross-linking techniques were also applied to the collagen conduit to enhance the mechanical properties. Tensile testing and burst pressure were the two measurements performed to characterize the mechanical integrity of the conduit. Mechanical characterization of the cross-linked collagen conduits identified 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride cross-linking as the most promising technique to reinforce the mechanical properties of native collagen. An oriented conduit of biocompatible material has been fabricated with decent mechanical strength and at a small diameter scale, which is especially applicable in engineering cardiovascular tissues and nerve grafts.

Phylogenetic analysis of North American Elymus and the monogenomic Triticeae (Poaceae) using three chloroplast DNA data sets.

Although the monogenomic genera of the Triticeae have been analyzed in numerous biosystematic studies, the allopolyploid genera have not been as extensively studied within a phylogenetic framework. We focus on North American species of Elymus, which, under the current genomic system of classification, are almost all allotetraploid, combining the St genome of Pseudoroegneria with the H genome of Hordeum. We analyze new and previously published chloroplast DNA data from Elymus and from most of the monogenomic genera of the Triticeae in an attempt to identify the maternal genome donor of Elymus. We also present a cpDNA phylogeny for the monogenomic genera that includes more data than, and thus builds on, those previously published. The chloroplast DNA data indicate that Pseudoroegneria is the maternal genome donor to all but one of the Elymus individuals. There is little divergence among the Elymus and Pseudoroegneria chloroplast genomes, and as a group, they show little divergence from the rest of the Triticeae. Within the monogenomic Triticeae, the problematic group Thinopyrum is resolved as monophyletic on the chloroplast DNA tree. At the intergeneric level, the data reveal several deeper-level relationships that were not resolved by previous cpDNA trees.