Critical care of sub-lethal irradiated transgenic mice using a complete soft food formula-DietGel76A™.

The objective of this research is to determine whether the administration of a complete soft food formula to sub-lethal irradiated animals from three different transgenic mouse strains over a period of 21 consecutive days will have a significant impact on the clinical signs, and the general survival rate of the animals. Our hypothesis is that using DietGel76A™, along with an antibiotic treatment, strict handling and manipulation procedures, the general mortality rate, as well as the onset of the clinical signs between the treated animals and the control animals, will be significantly lower. This hypothesis was confirmed for the C57BL/6 mice. However, the treatment with DietGel76A™ had only a very limited impact on the recovery of more irradiation sensitive strains (CD45.1 and mostly NRG). Further studies must be conducted on mice from these strains in order to assess whether mice belonging to more sensitive strains should be on DietGel76A™ for a longer period of time (at least 42days post irradiation).

Inhibition of constitutive signal transducer and activator of transcription 3 activation by novel platinum complexes with potent antitumor activity.

DNA-alkylating agents that are platinum complexes induce apoptotic responses and have wide application in cancer therapy. The potential for platinum compounds to modulate signal transduction events that contribute to their therapeutic outcome has not been extensively examined. Among the signal transducer and activator of transcription (STAT) proteins, Stat3 activity is frequently up-regulated in many human tumors. Various lines of evidence have established a causal role for aberrant Stat3 activity in malignant transformation and provided validation for its targeting in the development of small-molecule inhibitors as novel cancer therapeutics. We report here that platinum-containing compounds disrupt Stat3 signaling and suppress its biological functions. The novel platinum (IV) compounds, CPA-1, CPA-7, and platinum (IV) tetrachloride block Stat3 activity in vitro at low micromolar concentrations. In malignant cells that harbor constitutively activated Stat3, CPA-1, CPA-7, and platinum (IV) tetrachloride inhibit cell growth and induce apoptosis in a manner that reflects the attenuation of persistent Stat3 activity. By contrast, cells that do not contain persistent Stat3 activity are marginally affected or are not affected by these compounds. Moreover, CPA-7 induces the regression of mouse CT26 colon tumor, which correlates with the abrogation of persistent Stat3 activity in tumors. Thus, the modulation of oncogenic signal transduction pathways, such as Stat3, may be one of the key molecular mechanisms for the antitumor effects of platinum (IV)-containing complexes.

Assessing the risk of transmission of three infectious agents among mice housed in a negatively pressurized caging system.

Previous studies from our institution have shown that ventilated caging run at negative pressure to a mouse room dramatically reduced exposure of personnel to the major mouse allergen, Mus m 1. The current study was designed to determine whether negative cage ventilation posed an inordinate risk for spread of infectious agents between cages and/or racks. B6;129S-Tnfsf5(tm1Imx)/J (TNF) mice, which were naturally and persistently infected with Pneumocystis carinii, Helicobacter bilis, and Pasteurella pneumotropica, were used as the source of infections. Uninfected C3Smn.CB17-Prkdc(scid)/J (SCID) mice with severe combined immunodeficiency were used to detect transmission. The following methods were used to detect transmission of infections: polymerase chain reaction (PCR) amplification and histological examination of lungs for P. carinii; PCR of fecal specimens or cecal contents for H. bilis; and culture of oropharyngeal, tracheal, or vaginal swabs for P. pneumotropica. We determined whether transmission of the three agents occurred via direct contact (cohabitation), exposure to soiled bedding, and/or by handling naive SCID mice after handling infected TNF mice. During a 12-week period, all three infectious agents were readily transmitted to uninfected mice by cohabitation. Transmission was much less efficient and occurred later among mice exposed to contaminated bedding. Transmission did not occur as a result of handling. We then studied transmission of the three infectious agents among mice housed in individually ventilated cages run at negative pressure in a small, crowded mouse room. Transmission of P. carinii was detected at the end of the 12-month study in the densely populated room, probably because the exhaust from the changing station passed over soiled cages and caused aerosolization of particulates. Caging systems run at negative pressure effectively reduce personnel exposure to allergens and may also inhibit the transmission of infectious diseases.