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Mucin 1 (MUC1) is a transmembrane glycoprotein that is overexpressed in many tumor types, including breast, pancreatic, and ovarian cancer. The aim of this study was to create a construct containing sodium-iodide symporter (NIS) under the control of the 0.8-kb MUC1 promoter to infect pancreatic cancer cells both in vitro and in vivo, to investigate the potential for radioiodide imaging and ablation of this disease.We amplified the 797-bp MUC1 promoter by two-step nested PCR. Subsequently, a replication-deficient adenoviral construct was created containing the MUC1 promoter followed by the human NIS gene. Iodide uptake assays and immunofluorescence were used to confirm NIS expression and function. Pancreatic cancer xenografts in mice were infected with Ad/MUC1/NIS and then imaged and treated using radioiodide.A 23- and 15.5-fold increase in iodide uptake was observed in Ad/MUC1/NIS-infected MUC1-positive Capan-2 and SW1990 cells with no significant increase observed in MUC1-negative Hela cells or in cells infected with the control virus. The in vivo study showed a clear image of Ad/MUC1/NIS-infected tumor xenografts using (125)I. Administration of a therapeutic dose of (131)I resulted in a regression in size to 76 +/- 15% of their original volume, whereas control tumors continued to increase in size to200% of their original volume.These results show that the 0.8-kb MUC1 promoter was successfully used to drive human NIS-targeted expression in pancreatic cancer cells, and Ad/MUC1/NIS-mediated radiotherapy can make pancreatic cancer xenografts in mice shrinking. This could potentially have applications for both imaging and therapy in other MUC1-positive tumors.

Synergy between interleukin-12 (IL-12) and B7-1 (CD80) for cancer immunotherapy has previously been demonstrated in animal models of breast cancer, lymphoma, and multiple myeloma. With a view to human clinical application, tricistronic retroviral and adenovirus vectors co-expressing IL-12 (IL-12p40 plus IL-12p35) and CD80 were constructed by utilizing two internal ribosome entry site (IRES) sequences to link the three cDNAs. A murine stem cell virus (MSCV)-based retroviral vector (MSCV-hIL12.B7) utilized distinct IRES sequences from the encephalomyocarditis virus (EMCV) and the foot-and-mouth disease virus (FMCV), whereas Ad5-based adenovirus vectors contained transcriptional units with two EMCV IRES sequences under the control of murine (AdMh12.B7) or human (AdHh12.B7) cytomegalovirus promoters. AdMh12.B7 was found to consistently direct higher levels of IL-12 and CD80 expression than AdHh12.B7 following infection of a number of human tumor cell lines. In preclinical studies, the human myeloma cell line U266 was infected with MSCV-hIL12.B7 and a resulting clonal cell line, U/MSCV-h12.B7, was generated with stable expression of CD80 and secreting IL-12 at 1 ng/24 h/106 cells. By comparison, following AdMh12.B7 infection, 81% of infected U266 cells (U/AdMh12.B7) expressed CD80 and secreted IL-12 at 25–50 ng/24 h/106 cells. Both engineered myeloma cell lines stimulated enhanced allogeneic mixed lymphocyte proliferation and provoked increases in cytotoxic T-lymphocyte responses and γ-interferon release from normal donor lymphocytes exposed to parental U266 cells. These results suggest potential clinical utility of AdMh12.B7 in immunotherapy strategies for the treatment of multiple myeloma and other cancers. Cancer Gene Therapy (2001) 8, 361–370

Background Our aim was to summarize our experience with the diagnosis and surgical treatment of solid pseudopapillary neoplasm (SPN) of the pancreas to provide a reference for the management of this rare condition. Methods We collected and analyzed retrospective data on the clinical presentation, laboratory investigations, radiologic imaging, pathology and operative details of patients with SPN of the pancreas diagnosed between February 2001 and December 2009. Results In all, 23 of 24 patients were women, and the mean age of all patients was 31 years. The most common clinical presentation was vague abdominal pain. Abdominal imaging showed solid or solid cystic masses in the pancreas, mostly in the tail or head of the gland. All patients were treated surgically. There were no postoperative deaths. After follow-up ranging from 4 to 109 months (median 68 mo), 20 of 22 patients who underwent curative resection were alive with no evidence of disease recurrence. Of the 2 patients with R1 resections, 1 died 42 months after surgery, whereas the other underwent a second operation and was alive after 36 months' follow-up. Conclusion Solid pseudopapillary neoplasm of the pancreas is a relatively indolent tumour. The initial diagnosis of SPN of the pancreas is suggested by radiologic imaging findings but should be considered in the context of clinical and histopathologic characteristics. We advocate for complete surgical resection once SPN is diagnosed.

Recent research indicates that there is delayed development in the more central part of the auditory brainstem in very preterm babies. We aimed to study whether this is also the case for late preterm babies.The maximum length sequence brainstem auditory evoked response (MLS BAER) was used to study functional status of the auditory brainstem. Babies born at 33-36 week gestation and without any major perinatal complications were recruited. MLS BAER was recorded and analyzed at term age.No significant correlation was found between most MLS BAER variables and physiological factors (gender, postconceptional age, bodyweight, and head circumference obtained at time of testing). Wave latencies and amplitudes, and I-V and I-III intervals in the preterm babies were essentially similar to those in the term controls at all click rates. However, III-V interval increased significantly at 227-910/s clicks (p0.05-0.01). All latencies, amplitudes and intervals correlated significantly with click rates (all p0.001). No differences were found in the slopes of MLS BAER variables-rate functions between the later preterm babies and term controls.Babies born at 33-36 weeks gestation without major complications had an increased III-V interval at high-rate stimulation. This suggests that late preterm babies have a mild delay in neural conduction in the more central part of the auditory brainstem.