Trisomy 16 in a pigtailed macaque (M. nemestrina) with multiple anomalies and developmental delays

A female pigtailed macaque (Macaca nemestrina) with unusual physical characteristics, deficits in learning and cognitive tasks, abnormal social behavior, and abnormal reflexes and motor control was followed from birth until 3 years of age and found to have trisomy 16, which is homologous to trisomy 13 in humans. The animal described here showed similar features to cases of trisomy 16 and 18 (human trisomy 13 and 18, respectively) reported previously in nonhuman primates. However, both significant differences and similarities were found when compared with the homologous human trisomy. Evaluation of the genetic components of these disorders as well as systematic developmental evaluation can lead to new insights into the genetic basis of speciation, development, and the underlying differences between humans and their closest living relatives.     

Dog osteogenic sarcoma microvasculature observed with a Spälteholz technique

A well-distributed, patent microvascular network is essential for adequate, uniform delivery of chemotherapy into solid tumors. This network has not been evaluated in osteogenic sarcoma. Sp?lteholz tissue clarification was used to observe the microvasculature of canine humeri bearing osteogenic sarcoma. Freshly amputated limbs, obtained from therapeutic amputation, were infused with a micron-sized carbon particle solution, frozen, and then cut into sagittal and axial 0.5-mm thick sections. They were photographed, then radiographed using high resolution Faxitron xray, chemically treated to clarify the tissue, and then rephotographed. Microvasculature was identified by the localization of carbon particles, which were unaffected by the clarification process, within the clarified sections. Clarified section photographs were digitized to gray scale levels and analyzed using IMAGE software; levels are directly related to capillary density. Faxitron and original images were registered to the clarified images to identify tissue regions. Multiple regions of interest from normal muscle, fat, bone, and tumor regions were selected and averaged. The microvasculature of the tumor was inhomogeneous, whereas its density was considerably lower than normal adjacent muscle and bone (range, 56-72% lower). These findings suggest that insufficient microvascular density and distribution may provide additional explanation for the poor response of solid tumors to chemotherapy and radiation therapy.     

Prevention of thromboembolism after neurosurgery for brain and spinal tumors

OBJECTIVE: Deep venous thrombosis (DVT) is a major cause of morbidity and mortality after surgery for primary and metastatic brain tumors. METHODS: We conducted a confidential survey of American neurosurgeons interested in tumor surgery to assess DVT risk awareness and thromboprophylaxis patterns. RESULTS: Of the 172 respondents, 108 (63%) underestimated the DVT risk after brain tumor surgery. After operating on patients who had brain or spinal tumors, 81.4 and 78.5% of respondents, respectively, reported using DVT prophylaxis. After performing brain tumor surgery, 76.2% of respondents reported using solely mechanical methods of prophylaxis "always" or "most of the time." CONCLUSION: American neurosurgeons tend to underestimate the risk of DVT associated with brain tumor surgery and to use mechanical thromboprophylaxis despite the availability of effective pharmacologic antithrombotics. A better appreciation of the risk of thrombosis, combined with clinical studies to address safety, may enhance the use of prophylaxis and the perceived safety of antithrombotics in this setting.     

Infectivity enhanced, cyclooxygenase-2 promoter-based conditionally replicative adenovirus for pancreatic cancer

BACKGROUND AND AIMS: Pancreatic cancer is one of the most aggressive human malignancies. Conditionally replicative adenoviruses (CRAds) have shown some promise in the treatment of cancers. However, to date, their application for pancreatic cancer has met several obstacles: one is lack of a good control element to regulate replication, and the other is relatively low adenoviral infectivity. Thus, we constructed infectivity enhanced cyclooxygenase (COX)-2 promoter-based CRAds to develop a safe and effective therapeutic modality. METHODS: The CRAds were designed to achieve COX-2 promoter-controlled E1 expression for regulated replication (COX-2 CRAds). The infectivity-enhanced CRAds also have an RGD-4C motif in the adenoviral fiber-knob region. The selectivity and efficacy of these constructs were analyzed with cell lines in vitro. The in vivo therapeutic effect and viral replication were analyzed with a xenograft model. Pathology of the major organs and E1 RNA levels in the liver were also studied after systemic administration. RESULTS: The COX-2 CRAds showed a selective cytocidal effect in vitro in COX-2-positive cells and killed most of the pancreatic cancer cells. In vivo, intratumoral administration of the infectivity-enhanced COX-2 CRAds (10(9) particles) showed a strong antitumor effect comparable to wild-type virus, whereas the COX-2 CRAds without infectivity enhancement showed a limited effect. Viral replication was confirmed in the xenograft tumors. Systemic administration did not cause any detectable toxicity; the E1 RNA level in the liver after COX-2 CRAd administration was minimal. CONCLUSIONS: Infectivity-enhanced COX-2 CRAd is a promising agent for the treatment of pancreatic cancer.