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Cancer cells are able to proliferate at accelerated rates within the confines of a three-dimensional (3D) extracellular matrix (ECM) that is rich in type I collagen. The mechanisms used by tumor cells to circumvent endogenous antigrowth signals have yet to be clearly defined. We find that the matrix metalloproteinase, MT1-MMP, confers tumor cells with a distinct 3D growth advantage in vitro and in vivo. The replicative advantage conferred by MT1-MMP requires pericellular proteolysis of the ECM, as proliferation is fully suppressed when tumor cells are suspended in 3D gels of protease-resistant collagen. In the absence of proteolysis, tumor cells embedded in physiologically relevant ECM matrices are trapped in a compact, spherical configuration and unable to undergo changes in cell shape or cytoskeletal reorganization required for 3D growth. These observations identify MT1-MMP as a tumor-derived growth factor that regulates proliferation by controlling cell geometry within the confines of the 3D ECM.

In light of proposals to improve diets by shifting food prices, it is important to understand how price changes affect demand for various foods. We reviewed 160 studies on the price elasticity of demand for major food categories to assess mean elasticities by food category and variations in estimates by study design. Price elasticities for foods and nonalcoholic beverages ranged from 0.27 to 0.81 (absolute values), with food away from home, soft drinks, juice, and meats being most responsive to price changes (0.7-0.8). As an example, a 10% increase in soft drink prices should reduce consumption by 8% to 10%. Studies estimating price effects on substitutions from unhealthy to healthy food and price responsiveness among at-risk populations are particularly needed.

The prevalence of obesity, measured by body mass index, has risen to unacceptable levels in both men and women in the United States and worldwide with resultant hazardous health implications. Genetic, environmental, and behavioral factors influence the development of obesity, and both the general public and health professionals stigmatize those who suffer from the disease. Obesity is associated with and contributes to a shortened life span, type 2 diabetes mellitus, cardiovascular disease, some cancers, kidney disease, obstructive sleep apnea, gout, osteoarthritis, and hepatobiliary disease, among others. Weight loss reduces all of these diseases in a dose-related manner-the more weight lost, the better the outcome. The phenotype of "medically healthy obesity" appears to be a transient state that progresses over time to an unhealthy phenotype, especially in children and adolescents. Weight loss is best achieved by reducing energy intake and increasing energy expenditure. Programs that are effective for weight loss include peer-reviewed and approved lifestyle modification programs, diets, commercial weight-loss programs, exercise programs, medications, and surgery. Over-the-counter herbal preparations that some patients use to treat obesity have limited, if any, data documenting their efficacy or safety, and there are few regulatory requirements. Weight regain is expected in all patients, especially when treatment is discontinued. When making treatment decisions, clinicians should consider body fat distribution and individual health risks in addition to body mass index.

On the basis of our simulation models, childhood obesity and overweight will continue to be a major health problem in the United States. Early development of obesity predicted obesity in adulthood, especially for children who were severely obese. (Funded by the JPB Foundation and others.).

Policy makers seeking to reduce childhood obesity must prioritize investment in treatment and primary prevention. We estimated the cost-effectiveness of seven interventions high on the obesity policy agenda: a sugar-sweetened beverage excise tax; elimination of the tax subsidy for advertising unhealthy food to children; restaurant menu calorie labeling; nutrition standards for school meals; nutrition standards for all other food and beverages sold in schools; improved early care and education; and increased access to adolescent bariatric surgery. We used systematic reviews and a microsimulation model of national implementation of the interventions over the period 2015-25 to estimate their impact on obesity prevalence and their cost-effectiveness for reducing the body mass index of individuals. In our model, three of the seven interventions--excise tax, elimination of the tax deduction, and nutrition standards for food and beverages sold in schools outside of meals--saved more in health care costs than they cost to implement. Each of the three interventions prevented 129,000-576,000 cases of childhood obesity in 2025. Adolescent bariatric surgery had a negligible impact on obesity prevalence. Our results highlight the importance of primary prevention for policy makers aiming to reduce childhood obesity.

We created parabiotic mice, joining ROSA26 and PeP3 b animals, to study the trafficking of hematopoietic stem cells (HSCs) from marrow to blood and their return to marrow. The transfer of HSCs was assayed by secondary marrow transplantation and was 1.0% to 2.5% after 3, 6, 8, and 12 weeks. Thus, HSC homeostasis is primarily maintained by the retention of stem cells derived from replication events within the marrow, not the homing and engraftment of HSCs from the circulation. Of interest, the phenotypes of marrow progenitors and granulocytes were similar to those for HSCs, implying that the marrow functions as an intact compartment where differentiating cells derive from endogenous HSC. In contrast, 50% of splenic granulocytes and progenitor cells derived from the parabiotic partner, suggesting splenic progenitor cells were in constant equilibrium with progenitors in blood. In additional studies, animals were exposed to granulocyte-colonystimulating factor (G-CSF) and stem cell factor at days 17 to 20 of parabiosis and were studied 3 weeks later; 10.1% of marrow HSCs derived from the parabiotic partner. These data imply that HSCs, mobilized to the blood in response to cytokine exposure, are destined to later return to marrow, an observation that supports the concept that the mobilized peripheral blood stem cells used in clinical transplantation function physiologically. (Blood.