Serotonin transporter antagonists target tumor-initiating cells in a transgenic mouse model of breast cancer.

Accumulating data suggests that the initiation and progression of human breast tumors is fueled by a rare subpopulation of tumor cells, termed breast tumor-initiating cells (BTIC), which resist radiotherapy and chemotherapy. Consequently, therapies that abrogate BTIC activity are needed to achieve durable cures for breast cancer patients. To identify such therapies we used a sensitive assay to complete a high-throughput screen of small molecules, including approved drugs, with BTIC-rich mouse mammary tumor cell populations. We found that inhibitors of the serotonin reuptake transporter (SERT) and serotonin receptors, which include approved drugs used to treat mood disorders, were potent inhibitors of mouse BTIC activity as determined by functional sphere-forming assays and the initiation of tumor formation by transplant of drug-exposed tumor cells into syngeneic mice. Moreover, sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI), synergized with docetaxel (Taxotere) to shrink mouse breast tumors in vivo. Hence drugs targeting the serotonergic system might be repurposed to treat breast cancer patients to afford more durable breast cancer remissions.

Toward impacting medical and psychiatric comorbidities in persons with intellectual/developmental disabilities: an initial prospective analysis.

OBJECTIVE: The purpose of this study was to determine the effectiveness of psychiatric medical services, counseling, and behavioral treatments for adult patients with intellectual disabilities plus behavioral disorders and/or emotional distress. METHODS: Behavioral and medical data were collected at six and 12 months for a consecutive series of 141 adult patients with mild, moderate, or severe/profound intellectual disabilities who had been referred to a dual diagnosis mental health clinic, and treatment outcomes were compared. RESULTS: Most improvement in behavioral problem severity occurred at six months, then plateaued. Treatment improvement for subjects with anxiety disorders was statistically significant across all interventions. In this sample, as expected, patients with intellectual disability had higher incidences of medical illnesses than the general population. CONCLUSIONS: Subjects with more behavioral (overt) symptoms tended to receive referrals for behavioral support, and subjects with less overt symptoms were referred to counseling. In a follow-up study, similar individuals with moderate intellectual disabilities will be seen psychiatrically, but then randomly assigned to either supportive counseling or behavior support, or both. They will be followed prospectively, to determine the relative benefits of supportive psychotherapy, behavior support, or a combination, and for what duration of time the treatment should be continued.

Serotonin syndrome in the deployed setting.

Serotonin syndrome is a potential side effect of some psychotropic medications in common use today. With over 8000 adverse events related to this condition in 2004 alone, this risk warrants further attention. The deployed environment presents a unique set of stressors and risks involved in treatment with any psychotherapeutic agent. The following case illustrates one incidence of rapid titration of a selective serotonin reuptake inhibitor (SSRI) (fluoxetine) contributing to the emergence of serotonin syndrome.

A novel method for static equation-of state-development: equation of state of a cross-linked poly(dimethylsiloxane) (PDMS) network to 10 GPa.

Pressure-volume-temperature (PVT) equation-of-state (EOS) information for polymers and polymeric composites is valuable for predicting their response to extreme conditions. An obstacle in determining equations of state for polymeric materials is the lack of a simple, static experimental method for acquiring PVT data for solid networks and liquids at pressures greater than several kilobars. Here, we report a novel approach in determining static EOS for polymers using high-pressure diamond-anvil cells coupled with optical microscopy and image analysis. Results are presented for a cross-linked poly(dimethylsiloxane) polymer, Sylgard 184. Static isothermal results were fitted to empirical and semiempirical equations of state, including the Tait, Birch-Murnaghan, and Vinet forms. Static PV data were also converted to pseudoshock velocity-pseudoparticle velocity (U(s)-u(p)) for comparison to dynamic Hugoniot data. A linear Rankine-Hugoniot fit U(s)=s(T)u(p)+c(T) gives c(T)=1.572 km/s and s(T)=1.703. s(T) is related to the pressure derivative of the bulk modulus B(0) (') by s(T)=(B(0) (')+1)/4 and B(0) (')=5.8. A comparison of the static and shock data is given, along with an estimate of the Grüneisen parameter, and a discussion of the free volume content in the polymer network, and limitations of this novel method.