Vitamin A: evidence for its preventive role in human cancer.

Both the provitamin beta-carotene and natural vitamin A and its derivatives (the retinoids) are being proposed as potential chemopreventive agents. The biochemistry and pharmacology of vitamin A suggest a number of mechanisms whereby carcinogenesis can be affected. Epidemiologic studies have consistently demonstrated an increased relative risk of cancer for people with low vitamin A intake or low-to-normal serum retinol values. Chemoprevention trials in humans are only now beginning. In the interim, daily consumption of vitamin-A-containing foods may be a "prescription" worth following

Neonatal SSRI Exposure Programs a Hypermetabolic State in Adult Mice

Background. Selective serotonin reuptake inhibitor (SSRI) therapy complicates up to 10% of pregnancies. During therapy, SSRIs exert pleiotropic antidepressant, anorexigenic, and neurotrophic effects. Intrauterine SSRI exposure has been modeled by neonatal administration to developmentally immature rodents, and it has paradoxically elicited features of adult depression. We hypothesized neonatal SSRI exposure likewise programs a rebound hypermetabolic state in adult mice. Methods. C57BL/6 pups were randomized to saline or sertraline (5 mg/kg/d) from P1–P14. Because estrogen increases tryptophan hydroxylase 2 (TPH2) expression, a subset of female mice underwent sham surgery or bilateral ovariectomy (OVX). Metabolic rate was determined by indirect calorimetry. Results. In both male and female mice, neonatal SSRI exposure increased adult caloric intake and metabolic rate. SSRI-exposed female mice had significantly decreased adult weight with a relative increase in brain weight and melatonin excretion, independent of ovarian status. Cerebral cortex TPH2 expression was increased in SSRI-exposed male mice but decreased in OVX SSRI-exposed female mice. Conclusions. SSRI exposure during a critical neurodevelopmental window increases adult caloric intake and metabolic rate. Ovarian status modulated central TPH2 expression, but not adult energy balance, suggesting programmed neural connectivity or enhanced melatonin production may play a more important role in the post-SSRI hypermetabolic syndrome

Learning from the 'Lost Forty'

This thesis focuses on the reimagining of Riverside Park in Grand Rapids, Minnesota, to incorporate the principles of successional ecosystems found in the “Lost Forty” to produce a demonstration park that promotes walkability in a Midwestern town constrained by cold weather and automobile dominance

BENDAMUSTINE CONDITIONING REDUCES GVHD WHILE MAINTAINING GVL IN MURINE MHC-MISMATCHED HEMATOPOIETIC CELL TRANSPLANTATION

Graft-versus-host disease (GvHD) remains a significant obstacle to the success of hematopoietic stem cell transplantation due to challenges in uncoupling GvHD from the highly beneficial graft-versus-leukemia (GvL), both of which are mediated by donor T-cells. Our laboratory has previously shown that pre-transplant conditioning with bendamustine (BEN) and total body irradiation (TBI) significantly reduces GvHD when compared to cyclophosphamide (CY)+TBI in a major histocompatibility complex (MHC) mismatched murine bone marrow transplant model. Despite reduced GvHD, conditioning with BEN+TBI retains GvL effects in mice with A20-luciferase. To determine which cells are responsible for this GvL effect, CD4+ and CD8+ T-cells and NK cells were depleted. We see the greatest deficit in anti-tumor effect when CD8+ T-cells are depleted, followed by CD4+ T-cells, with depletion of NK cells showing little change to GvL effects. This indicates that CD8+ T-cells primarily contribute to the GvL effect seen in this model. As GvHD and GvL are mediated by donor T-cells, whose effector functions are informed by dendritic cells (DCs), we characterized DCs that were conditioned with BEN+TBI compared to CY+TBI to understand the mechanism of BEN. We hypothesized that BEN inhibits STAT3 signaling causing a compensatory increase in Flt3 and Akt1 expression to increase signaling through this alternative pathway. Contrary to our hypothesis, the qRT-PCR results showed a significant decrease in Akt1 transcripts in both mice and humans as the concentration of BEN increased

First-line therapy for non-small cell lung cancer including targeted therapy: A brief review

Operative removal of non-small cell lung cancer remains the mainstay of therapy. When this is not possible, cytotoxic chemotherapy and/or radiotherapy can be given but are marginally effective in prolonging overall survival. However, with a better understanding of the pathobiology of the lung cancer cells, new targeted therapies have been developed which may produce dramatic responses in selected patients. This brief review will emphasize these newer therapies in this rapidly evolving field

December 2012 pulmonary case of the month: applying genetics

No abstract available. Article truncated after first page. History of Present Illness A 65 year old woman presented to her physician in with upper abdominal pain in August, 2007. A CT scan of the abdomen demonstrated no abnormalities in her abdomen, but a 3.7 x 2.4 cm mass in the left lower lobe was noted. PMH, FH and SH She has no significant prior medical history. She is a life-long nonsmoker. There is no significant family history. Physical Examination Her physical examination is unremarkable. Which of the following is true? 1.Lung cancer does not occur in nonsmokers 2.The lesion is likely a rounded pneumonia based on its size 3.A family history of lung cancer is not associated with an increase in lung cancer 4.Calcification of the mass usually indicates lung cancer 5.Adenocarcinoma is the most common lung cancer seen in nonsmokers